With the rapid rise in the number of therapeutic options for men with castration-resistant prostate cancer (CRPC) comes increasingly complicated treatment decision-making, emphasizing the need for biomarkers that can identify appropriate patients for specific treatments and accurately assess benefit. While prognostic factors describe natural history, predictive biomarkers are factors related to the disease or the host that are associated with improvements in outcomes, such as survival, due to specific therapies. Surrogate biomarkers provide an early estimate of treatment effect as an intermediate endpoint for outcomes such as survival. Such biomarkers have become of increasing importance in oncology to maximize the benefits of novel systemic agents while minimizing the harms to individual patients and the costs to society. Given the number of newly approved and expensive systemic therapies, including novel hormonal therapies, chemotherapies, immunotherapies, and bone microenvironment-targeting therapies, predictive biomarkers are needed to give physicians a more rational sense of matching the right patient to the right therapy sequence at a given time. Here I discuss prognostic and potential predictive biomarkers in men with CRPC and discuss their potential role in the management of men with metastatic disease. Learning objectives: 1. Define prognostic and predictive biomarkers and apply this knowledge to metastatic prostate cancer patients based on established biomarkers in the castration-resistant setting. 2. Understand the role of surrogate biomarkers in drug development, particularly with respect to metastatic prostate cancer.