Background There are well over a million homeless people in Western Europe and North America, but reliable estimates of the prevalence of major mental disorders among this population are lacking. We undertook a systematic review of surveys of such disorders in homeless people. Methods and Findings We searched for surveys of the prevalence of psychotic illness, major depression, alcohol and drug dependence, and personality disorder that were based on interviews of samples of unselected homeless people. We searched bibliographic indexes, scanned reference lists, and corresponded with authors. We explored potential sources of any observed heterogeneity in the estimates by meta-regression analysis, including geographical region, sample size, and diagnostic method. Twenty-nine eligible surveys provided estimates obtained from 5,684 homeless individuals from seven countries. Substantial heterogeneity was observed in prevalence estimates for mental disorders among the studies (all Cochran's χ2 significant at p < 0.001 and all I 2 > 85%). The most common mental disorders were alcohol dependence, which ranged from 8.1% to 58.5%, and drug dependence, which ranged from 4.5% to 54.2%. For psychotic illness, the prevalence ranged from 2.8% to 42.3%, with similar findings for major depression. The prevalence of alcohol dependence was found to have increased over recent decades. Conclusions Homeless people in Western countries are substantially more likely to have alcohol and drug dependence than the age-matched general population in those countries, and the prevalences of psychotic illnesses and personality disorders are higher. Models of psychiatric and social care that can best meet these mental health needs requires further investigation., Seena Fazel and colleagues show, through a systematic review and meta-regression analysis, that homeless people in Western countries have a higher prevalence of alcohol and drug dependence and mental disorders., Editors' Summary Background. In 2007, it was estimated that there were more than 1 million homeless people worldwide. The true magnitude of the problem is difficult to estimate with no internationally agreed definition for homelessness and with the different approaches taken by countries and organizations in counting homeless people. What we do know is that this is a diverse group of people who have poorer physical and mental health than the general population, leading to premature death. We also know that addressing barriers to health care and behavioral interventions for alcohol and drug dependence and mental health problems in this population can lead to lasting health gains. Why Was This Study Done? Health care for the homeless is a major public health challenge. Public policy and health service development depend on reliable estimates of the prevalence (how common a particular characteristic, e.g., a disease, is in a specific group of people or a specific population) of illnesses. By using statistical methods, the researchers aimed to provide a quantitative synthesis of the available evidence on mental health problems in this population and explore reasons for the differences in reported prevalence rates of serious mental disorders between studies, neither which have been done previously. What Did the Researchers Do and Find? The researchers systematically searched for surveys that estimated the prevalence of mental disorders in homeless people. Their final sample of 29 studies included a total of 5,684 homeless individuals based in the US, UK, mainland Europe, and Australia. Their main finding was that the prevalences of serious mental disorders were raised compared with expected rates in the general population, and many orders of magnitude higher than age-matched community estimates for psychosis, alcohol dependence, and drug dependence. In addition, the analysis found that alcohol and drug dependence is the most common mental disorder in the homeless (compared to psychosis, depression, and personality disorder). Also, the prevalence estimates of psychosis were found to be as high as those for depression. This latter finding contrasts with community estimates and other “at risk” populations such as prisoners and refugees, where depression is more common. The authors found substantial variation in the prevalence rates for these various disorders, and demonstrated that participation rates were associated with these variations for psychosis, depression, and personality disorder and that studies conducted more recently reported higher rates of alcohol dependence. What Do These Findings Mean? This review raises a number of implications for health services for the homeless and research for this population. First, traditional models of service delivery, which focus on those with severe mental illness, may not meet the mental health needs of most homeless people who suffer from alcohol and drug dependence and personality disorder. Second, an integrated approach to treatment may be beneficial and should take into account mental health, alcohol and drug abuse, welfare, and housing needs. Finally, future research should include studies that follow a group over time to help us better understand the risks and pathways into (and out of) homelessness, particularly in non-Western populations where there appears to be a paucity of information. Additional Information. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050225. This study is further discussed in a PLoS Medicine Perspective by Helen Herrman “How can health care systems effectively deal with the major health care needs of homeless people?” is a WHO initiative aimed at tackling the health care needs of homeless people FEANTSA, the European Federation of National Organizations Working with the Homeless, is an umbrella of not-for-profit organizations that participate in or contribute to the fight against homelessness in Europe The National Alliance to End Homelessness is a nonpartisan, mission-driven organization committed to preventing and ending homelessness in the US Information and good practice solutions for the homelessness service sector in Australia can be found on the National Homelessness Information Clearinghouse Web site Homeless Link is the national membership organization for frontline homelessness agencies in England with a mission to catalyze an end to homelessness Homeless Man Speaks provides an “on-the-street” perspective