This study examined the explanatory models of depression, perceived relationships between diabetes and depression, and depression treatment experiences of low-income, Spanish-speaking, Hispanics with diabetes and depression. A purposive sample (n=19) was selected from participants enrolled in a randomized controlled trial conducted in Los Angeles, California (United States) testing the effectiveness of a health services quality improvement intervention. Four focus groups followed by 10 in-depth semi-structured qualitative interviews were conducted. Data were analyzed using the methodology of coding, consensus, co-occurrence, and comparison, an analytical strategy rooted in grounded theory. Depression was perceived as a serious condition linked to the accumulation of social stressors. Somatic and anxiety-like symptoms and the cultural idiom of nervios were central themes in low-income Hispanics' explanatory models of depression. The perceived reciprocal relationships between diabetes and depression highlighted the multiple pathways by which these two illnesses impact each other and support the integration of diabetes and depression treatments. Concerns about depression treatments included fears about the addictive and harmful properties of antidepressants, worries about taking too many pills, and the stigma attached to taking psychotropic medications. This study provides important insights about the cultural and social dynamics that shape low-income Hispanics' illness and treatment experiences and support the use of patient-centered approaches to reduce the morbidity and mortality associated with diabetes and depression.