In recent years, there has been a marked increase in the number of approved therapies that increase survival of patients with castration-resistant prostate cancer. Current treatment guidelines provide therapeutic management recommendations, but these are primarily based on clinical factors such as performance status or site of metastasis (bone vs. visceral), and not on underlying molecular or cellular features of disease that may predict response. The ability to tailor treatment based on molecular or cellular features of disease could potentially reduce the occurrence of unnecessary side effects and ineffective treatments, and thereby reduce both direct and indirect medical costs. As such, it is important to identify and validate new prognostic and predictive molecular biomarkers that can be used to direct cancer treatment. This review will focus on existing and potential biomarkers in the context of castration-resistant prostate cancer management and discuss the need for continued discovery and validation of new biomarkers and biomarker panels for prostate cancer.