In June 1991 William Kennedy Smith received his Medical Degree from Georgetown University Medical School.   In 1992, as a physician, he worked with the International Medical Corps in Somalia. After completing a tour of orthopedic programs in Bosnia, South Africa, Mozambique and Angola (in cooperation with the International Medical Corps and the International Committee of the Red Cross) Smith founded Physicians Against Land Mines (PALM) in 1996. The goal of PALM was to ban the use and sale of land mines through supporting the international law banning antipersonnel land mines. Awareness of the crisis was accomplished through educational activities and advocacy initiatives. Community outreach activities highlight the need for appropriate prosthetic technologies, programs, and policies that will help land mine survivors productively reintegrate into society. In 1997, PALM, a member of the International Campaign to Ban Land Mines, was a co-recipient of the Nobel Peace Prize. Through PALM's activities in the area of landmine victim assistance, the scope of work of the organization expanded to include rehabilitation services and advocacy for people with disabilities worldwide. This expansion brought about the November 1998 launch of the Chicago-based Center for International Rehabilitation (CIR) that absorbed the important work of PALM as one of its key programs.

The CIR is engaged in educational initiatives and the development of prosthetics technology to improve rehabilitation service provision in developing countries. It operates a Rehabilitation Engineering Research Center (RERC) on Improved Technology Access for Landmine Survivors that has been designated a national center of excellence in rehabilitation engineering by the National Institute of Disability and Rehabilitation Research, which funds its operation. By developing and disseminating new technologies and techniques, the RERC works to improve access to mobility aids for landmine survivors and other amputees. It conducts research, development and training activities to explore appropriate technology solutions and build capacity within developing countries. The RERC also provides outreach and technology transfer to partner centers around the world through training workshops and international conferences. From 1999-2003, Smith served as principle investigator of the National Institute on Disability and Rehabilitation Research's Rehabilitation Engineering Research Center on improved technology access for landmine survivors.

With Smith as president, the CIR developed the world's first distance learning program in prosthetics, orthotics and amputee care in 2001. This program harnesses the power of the Internet to deliver world-class medical education to workers in clinics and hospitals in some of the poorest regions in the world. It uses a tailored mix of educational materials, including texts, electronic interactive media and face-to-face workshops, which are designed to reach the largest number of students in the most cost-effective manner. Courses have been taught in six countries to over 70 students from 30 rehabilitation centers. The centers in which these students are employed treat an estimated 8,600 war wounded and other amputees each year.

The CIR has become an established member of a global community of individuals and institutions working to improve the lives of people with disabilities around the world. In 2003, under Smith’s direction, it created the International Disability Rights Monitor (IDRM) -- an international grassroots research project designed to document and assess the status of persons with disabilities worldwide in order to promote their full inclusion and participation in society, as well as to advance the use of international humanitarian and disability law to ensure that their rights are respected and enforced. Since its inception, the IDRM has released a series of reports that draw a comparative analysis of living conditions, legal protections, education, employment, accessibility, health and housing services for people with disabilities. These reports, as well as other CIR activities, helped support efforts leading up to the passage of the 2006 United Nations (UN) Convention on the Rights of Persons with Disabilities. Through IDRM, the CIR has created a network of researchers in over 45 countries who systematically collect data and report on the progress, problems and barriers experienced by people with disabilities.

Independent mobility is a critical factor for inclusion in education and employment, but unfortunately many of the wheelchairs available in low-income countries are simply not durable enough for the environment and quickly become unusable. In response to this need, Smith and CIR staff collaborated with renowned engineer Ralf Hotchkiss of Whirlwind Wheelchair International to design a new wheelchair appropriate for rugged environments. In the summer of 2005, they conducted a four-month research study in Kabul, Afghanistan. Local physiotherapists and technicians received direct, hands-on training, and, in addition to wheelchair assembly, instruction was provided on user assessment, fitting and training. Upon completion of the workshop, participants worked in teams to issue 100 CIR-Whirlwind Wheelchairs to local users. Each wheelchair recipient was trained on the safe and efficient use of the chair, and had follow-up appointments for interviews and wheelchair inspections to measure durability.

Also in 2005, Smith formally launched the International Disability Educational Alliance Network (IDEAnet) website through the CIR. IDEAnet is a global collaboration of individuals and institutions that provide medical services and humanitarian relief. Like the CIR, it has a particular focus on disability in low-income and conflict-affected countries. Its mission is to foster collaborative efforts to use distributed learning and telemedicine to address health disparities and foster effective, sustainable health services. Through tools such as discussion forums, chats and document sharing, the IDEAnet website enables community members to share ideas and knowledge, enhance their skills and generate strategies and innovations that will help to improve health services around the globe. In addition, the flexible structure of the site allows members to collaborate on ongoing projects and, if they wish, start their own.

The newest initiative of the CIR is iCons in Medicine. In 2008, Smith officially launched the program which is a global telehealth and humanitarian Internet medicine volunteer alliance that connects health care providers in remote and medically underserved areas with a network of committed specialty physician volunteers who provide clinical support.

Independent from the CIR and IDEAnet, Smith opened MedRed in the fall of 2004. MedRed’s mission is to save lives and prevent suffering by making medical knowlege accessible to patients and healthcare providers at the point of care wherever medicine is practiced. MedRed uses the latest in information and communication technology to allow patients and healthcare providers to work together to maintain and access the most accurate and up to date health care knowledge from anywhere in the world. It also provides tools to help manage both everyday and emergency healthcare needs.