In the European Union, more than 400,000 individuals are homeless on any one night and more than 600,000 are homeless in the USA. The causes of homelessness are an interaction between individual and structural factors. Individual factors include poverty, family problems, and mental health and substance misuse problems. The availability of low-cost housing is thought to be the most important structural determinant for homelessness. Homeless people have higher rates of premature mortality than the rest of the population, especially from suicide and unintentional injuries, and an increased prevalence of a range of infectious diseases, mental disorders, and substance misuse. High rates of non-communicable diseases have also been described with evidence of accelerated ageing. Although engagement with health services and adherence to treatments is often compromised, homeless people typically attend the emergency department more often than non-homeless people. We discuss several recommendations to improve the surveillance of morbidity and mortality in homeless people. Programmes focused on high-risk groups, such as individuals leaving prisons, psychiatric hospitals, and the child welfare system, and the introduction of national and state-wide plans that target homeless people are likely to improve outcomes.