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This chapter describes the epidemiology of homelessness and mental illness in the United States, and explores some of the unique factors faced by this population. Psychiatric illness, particularly schizophrenia, bipolar disorder, and major depression, have a high prevalence in the homeless population. High rates of alcohol and substance abuse in the homeless population compound the psychiatric and medical problems. Homeless persons use the emergency department (ED) at a higher rate than non-homeless. The assessment of homeless patients with psychiatric complaints follows a process similar to domiciled persons. There are several areas in which the patient's homeless status should be given special consideration. The chapter discusses these considerations and further illustrates them using case studies. It concludes by discussing the process of assessing and providing care for these patients while reflecting on systemic challenges for improving emergency care for patients with homelessness and mental illness.