The objective of this paper is to profile the role of homelessness in drug and sexual risk in a population of young men who have sex with men (YMSM). Data are from a cross-sectional survey collected between 2000 and 2001 in New York City (N = 569). With the goal of examining the import of homelessness in increased risk for the onset of drug and sexual risk, we compare and contrast three subgroups: (1) YMSM with no history of homelessness, (2) YMSM with a past history of homelessness but who were not homeless at the time of the interview, and (3) YMSM who were currently homeless. For each group, we describe the prevalence of a broad range of stressful life events (including foster care and runaway episodes, involvement in the criminal justice system, etc.), as well as selected mental health problems (including past suicide attempts, current depression, and selected help-seeking variables). Additionally, we examine the prevalence of selected drug and sexual risk, including exposure to a broad range of illegal substances, current use of illegal drugs, and prevalence of lifetime exposure to sex work. Finally, we use an event history analysis approach (time-event displays and paired t-test analysis) to examine the timing of negative life experiences and homelessness relative to the onset of drug and sexual risk. High levels of background negative life experiences and manifest mental health distress are seen in all three groups. Both a prior experience of homelessness and currently being homeless are both strongly associated with both higher levels of lifetime exposure to drug and sexual risk as well as higher levels of current drug and sexual risk. Onset of these risks occur earlier in both groups that have had an experience of housing instability (e.g., runaway, foster care, etc.) but are delayed or not present among YMSM with no history of housing instability. Few YMSM had used drug prior to becoming homeless. While causal inferences are subject to the limitations of a cross-sectional design, the findings pose an empirical challenge to the prevailing assumption that prior drug use is a dominant causal factor in YMSM becoming homeless. More broadly, the data illustrate the complexity of factors that must be accounted for, both in advancing our epidemiological understanding of the complexity of homelessness and its relationship to the onset of drug and sexual risk among high risk youth populations. (c) 2005 The Association for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.