This study examined the association between perceived neighborhood safety and depressive symptoms among 443 out-of-treatment African American crack cocaine users interviewed between 2000 and 2002 in North Carolina and tested the regression of depression on perceived neighborhood safety and common predictors of depression. Perceived neighborhood safety was an important predictor of depressive symptoms in models that adjusted for other correlates of depression. The findings are limited by the cross-sectional nature of the data and the complex etiology and course of depression. Additional research is needed to clarify the relationship between perceived neighborhood safety and depression. The study was supported by the National Institute on Drug Abuse.