There has been significant progress in personalized drug development. In large part, this has taken place in the oncology field and been due to the ability of researchers/clinicians to discover and develop novel drug development tools (DDTs), such as biomarkers. In cancer treatment research, biomarkers have permitted a more accurate pathophysiological characterization of an individual patient, and have enabled practitioners to target mechanistically the right drug, to the right patient, at the right time. Similar to cancer, patients with substance use disorders (SUDs) present clinically with heterogeneous symptomatology and respond variably to therapeutic interventions. If comparable biomarkers could be identified and developed for SUDs, significant diagnostic and therapeutic advances could be made. In this review, we highlight current opportunities and difficulties pertaining to the identification and development of biomarkers for SUDs. We focus on cocaine dependence as an example. Putative diagnostic, pharmacodynamic (PD), and predictive biomarkers for cocaine dependence are discussed across a range of methodological approaches. A possible cocaine-dependent clinical outcome assessment (COA)--another type of defined DDT--is also discussed. At present, biomarkers for cocaine dependence are in their infancy. Much additional research will be needed to identify, validate, and qualify these putative tools prior to their potential use for medications development and/or application to clinical practice. However, with a large unmet medical need and an estimated market size of several hundred million dollars per year, if developed, biomarkers for cocaine dependence will hold tremendous value to both industry and public health.