This article investigates the life conditions that contribute to low-income fathers' depression and that may jeopardize their relationships with their children. This work is based on a cultural-ecological framework that emphasizes the need to understand these fathers within their larger familial and social contexts. The sample consisted of 127 predominantly African American participants in two urban and rural responsible fatherhood programs. Of the fathers, 56% reported depressive symptoms indicating cause for clinical concern. In addition, fathers resource challenges (unemployment; inability to pay full amount of child support order; limited access to reliable transportation; lack of permanent housing; problems with alcohol or drugs; health problems or disability; and criminal conviction history), residence (rural vs. urban), and level of social support were all significant predictors of fathers depression. The authors discuss how these findings can be used to guide future programmatic and policy initiatives pertaining to low-income, nonresidential fathers.