Four hundred forty-three impoverished medical patients, many of whom were homeless, were studied to determine whether homelessness is an independent predictor of current substance use. Twenty-four percent of the sample of patients were frequent alcohol users (i.e., daily or almost daily), and 18% had recently used illegal drugs (cocaine, heroin, PCP, LSD). Marijuana use was not included in the drug use variable. Bivariate analyses revealed that frequent alcohol was associated with being homeless, male, less educated, a veteran, unemployed, and having more children. Frequent alcohol users also were more likely to be sexually active, have had suicidal thoughts, a previous psychiatric hospitalization or felony conviction, an accident or injury, and poor physical health. Self-reported use of illegal drugs was associated with being younger, U.S. born, never married, having a poor mood, and a mental health problem or substance use by a parent. Use of illegal drugs was associated with being homeless, male, less educated, sexually active, and having a previous felony conviction or psychiatric hospitalization. Once demographic and family characteristics were controlled for, housing status was not related to either frequent alcohol or illegal drug use. Substance use among impoverished patients was a reflection of their historical social backgrounds rather than of their current housing status. Helping these patients to obtain stable housing may not impact the substance use of homeless persons.