MSF operates independently of any political, military, or religious agendas. Medical teams conduct evaluations on the ground to determine a population's medical needs before opening programs. The key to MSF’s ability to act independently in response to a crisis is its independent funding. Eighty-nine percent of MSF's overall funding (and 100 percent of MSF-USA's funding) comes from private sources, not governments. In 2006, MSF had more than three million individual donors and private funders worldwide.

MSF is neutral. The organization does not take sides in armed conflicts, provides care on the basis of need alone, and pushes for increased independent access to victims of conflict as required under international humanitarian law.

At times, MSF may speak out publicly in an effort to bring a forgotten crisis to public attention, to alert the public to abuses occurring beyond the headlines, or to challenge the diversion of humanitarian aid for political interests.