Much of our understanding of substance abuse and homelessness comes from data from the 1980s and may not necessarily reflect issues or trends prevalent during the 1990s. We report data from a two-city, community-based, populations-proportionate sample of 531 randomly selected homeless adults; the study was conducted in 1997 and compared substance-abusing to non-substance-abusing respondents. Most (78.3%) met criteria for substance abuse/dependence and were abusing either cocaine or alcohol and cocaine (68.5%). In the multiple logistic regression model, male gender (odds ratio [OR] 2.94, 95% confidence interval [CI] 1.70-5.09), less than a 12th grade education (OR 1.96, 95% CI 1.11-3.46), hustling or stealing for sustenance (OR 3.14, 95% CI 1.15-8.55), and identifying a need to learn how to manage one's money (OR 2.41, 95% CI 1.45-3.98) were independently associated with substance abuse/dependence. Drug abuse/dependence and polysubstance use among urban homeless persons became a more prevalent issue in the late 1990s. These individuals have unique needs that will require tailored interventions.