Over the past decade, at least 600,000 refugees from more than 60 different countries have been resettled in the United States. The personal history of a refugee is often marked by physical and emotional trauma. Although refugees come from many different countries and cultures, their shared pattern of experiences allows for some generalizations to be made about their health care needs and challenges. Before being accepted for resettlement in the United States, all refugees must pass an overseas medical screening examination, the purpose of which is to identify conditions that could result in ineligibility for admission to the United States. Primary care physicians have the opportunity to care for members of this unique population once they resettle. Refugees present to primary care physicians with a variety of health problems, including musculoskeletal and pain issues, mental and social health problems, infectious diseases, and longstanding undiagnosed chronic illnesses. Important infectious diseases to consider in the symptomatic patient include tuberculosis, parasites, and malaria. Health maintenance and immunizations should also be addressed. Language barriers, cross-cultural medicine issues, and low levels of health literacy provide additional challenges to caring for this population. The purpose of this article is to provide primary care physicians with a guide to some of the common issues that arise when caring for refugee patients.