We examined risk and protective factors associated with three qualitatively different drug use constructs describing a continuum of drug use among a sample of 1,179 homeless women. Relationships among positive and negative sources of social support, positive and negative coping strategies, depression, and the drug constructs of current drug use, drug problems, and physical drug dependence were assessed using structural equation models with latent variables. Current drug use was predicted by more negative social support (from drug-using family/friends), depression, and less positive coping. Drug Problems were predicted by more negative coping, depression, and less positive coping. Physical Drug Dependence was predicted by more negative social support and depression, and less positive social support. Results highlighted the importance of investigating both the positive and negative dimensions of psychosocial functioning, while suggesting that empowering homeless women and offering tangible resources for coping with the stress of being homeless may be beneficial to them.