The objective of this study is to examine the relationship between depression and drug use and potential ramifications of that relationship on the health services needs, utilization, and costs of chronic and injecting drug abusers. A network-based sample of 1,330 injecting and other chronic drug users, as well as non-drug using neighborhood controls, was obtained within Dade County, Florida. Using the Health Services Research Model as an analytical framework, results show that drug users had significantly higher levels of depression than non-drug users from similar neighborhoods. In addition, it was found that depression was significantly associated with perceptions of poor health, increased health problems, and perceived limitations on even light physical activity among both drug users and non-users. Among drug users, depression was also significantly related to not receiving needed care, lack of treatment adherence, use of the emergency room for primary care or any reason, hospital admissions, and any use of outpatient or private clinic services. Results from logistical regression analysis show that even when controlling for relevant issues such as sociodemographic, economic, and drug use variables, depression retains an independent and significant relationship with health services need and utilization. Differences in the cost of health care utilization between depressed and non-depressed samples are also estimated. Implications of this study point to the need to consider screening and treatment for depression within health system structures in order to improve cost-effective access to needed services among drug using populations.