While personal and organizational challenges occur in every area of health care, practitioners of international medicine face unique problems and dilemmas that are rarely discussed in training programs. Health professions schools, residency and fellowship programs, nongovernmental organizations (NGOs), and government programs have a responsibility to make those new to international medicine aware of the special circumstances that they may face and to provide methods for understanding and dealing with these circumstances. Standard "domestic" approaches to such challenges may not work in international medicine, even though these challenges may appear to be similar to those faced in other clinical settings. How should organizations ensure that well-meaning health intervention efforts do not cause adverse unintended sequelae? How should an individual balance respect for cultural uniqueness and local mores that may profoundly differ from his or her own beliefs, with the need to remain a moral agent true to one's self? When is acceptance the appropriate response to situations in which limitations of resources seem to preclude any good solution? Using a case-based approach, the authors discuss issues related to the four major international medicine domains: clinical practice (postdisaster response, resource limitations, standards of care), medical systems and systems development (prehospital care, wartime casualties, sustainable change, cultural awareness), teaching (instruction and local resources, professional preparation), and research (questionable funded studies, clinical trials, observational studies). It is hoped that this overview may help prepare those involved with international medicine for the challenges and dilemmas they may face and help frame their responses to these situations.