Homeless men, women, and children make up a growing population that is vulnerable to preventable disease, progressive morbidity, and premature death. Homelessness and poverty are inextricably linked, and subgroups of persons who live in poverty have a particularly high risk for becoming homeless. Providing effective primary care for homeless persons is a formidable task because of many internal and external barriers to care. Targeted care strategies and new approaches to primary care are required to lower these barriers. Effective disease prevention in the homeless requires effective programs and policies to prevent homelessness. It is imperative that health professionals, the societies to which they belong, and academic health systems reaffirm their social responsibility, commit to changing public policies that perpetuate homelessness, and assist in the development and provision of primary health care services for persons who are homeless or on the brink of homelessness.