After extensive field experience with Médecins Sans Frontières/Doctors Without Borders (MSF), James was elected MSF's international president from 1998 to 2001. In 1999, he launched MSF's Access to Essential Medicines Campaign and in that same year, accepted the Nobel Peace Prize on behalf of MSF for its pioneering approach to medical humanitarianism, particularly for its approach to witnessing. James worked as MSF's Head of Mission in Goma, Zaire, in 1996-1997, during the refugee crisis. He was MSF's Head of Mission in Kigali during the 1994 Rwandan genocide and MSF's medical co-coordinator in Baidoa, Somalia, during the civil war and famine of 1992-1993. James' first MSF mission was in Peru in 1992. For his medical humanitarian leadership in Rwanda during the 1994 genocide, he was awarded the meritorious Service Cross, Canada's highest civilian award.
As international president, James represented MSF in numerous humanitarian emergencies and on critical humanitarian issues in, among others: Sudan, Kosovo, Russia, Cambodia, South Africa, India and Thailand. He also represented MSF in many national parliaments as well as international organizations such as the United Nations High Commissioner for Refugees.
From 2001 to 2004, James co-chaired MSF's Neglected Diseases Working Group, responsible for launching the Drugs for Neglected Diseases Initiative. In 2004, he became a research scientist at St. Michaels' Hospital in Toronto, Canada, and an associate professor of both medicine and political science at the University of Toronto. In 2006, one of the world's leading medical journals, The Lancet, recognized one of Orbinski's co-authored papers on HIV/AIDS treatment adherence as among the 20 most significant medical research papers in the world. Another of his co-authored papers, which appeared in the The Lancet in 2002, is recognized as "one of the most important scholarly articles that shaped scholarship in the field of global health in the post Second World War years."
James received his M.D. from McMaster University in 1990, and held a Medical Research Council of Canada fellowship to study pediatric HIV in sub-Saharan Africa. He completed an M.A. in international relations at the University of Toronto in 1998 before being elected international president of MSF.
In 2004, he co-founded Dignitas International, an interdisciplinary academic non-governmental organization that is now a leading medical humanitarian organization in the development of solutions for global health.
Triage, James' award-winning and internationally acclaimed documentary film on medical humanitarianism, was screened at the 2008 Sundance Film Festival, and won the 2008 Amnesty International Gold Medal Award. In 2011, Triage was incorporated into the "War and Medicine" exhibit at the Canadian War Museum in Ottawa, Canada. released internationally in 2008, Orbinski's bestselling book, An Imperfect Offering: Humanitarianism in the Twenty-First Century has been translated into five languages. It won the 2009 Writer's Trust Shaunessy-Cohen Prize for best political writing in Canada, was one of five books nominated for the 2008 Canadian Governor General's Literary Award in non-fiction and was one of National Public Radio's 2008 top five political and current affairs books in the United States.
- An Imperfect Offering: Humanitarianism in the Twenty-First Century. Toronto: Anchor Canada, 2009.
- Canadian Civil Liberties Association Award for Excellence, 2012
- Queen Elizabeth II Diamond Jubilee Medal, 2012
- The Canadian Bar Association's Walter S. Tarnopolsky Human Rights Award, 2011
- Order of Ontario, 2010
- Officer of the Order of Canada, 2009
- Writer's Trust Shaunessy-Cohen Prize, 2009
- Service Cross, Canada