Homeless individuals suffer from a constellation of health issues, experience barriers to medical care that are both recognizable and hidden, and score worse on measures of health outcomes than the general population. They differ to such an extent from the general population that homeless people should be viewed by clinicians as a unique patient population. Improving the health of this population is difficult for a number of reasons. This article explores those reasons. It describes common conditions affecting homeless people and discusses how patient-centered comprehensive primary care, collaboration between health care providers and social service organizations, and innovative delivery of medical respite services can result in better care for this population.