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Prostate cancer is one of the most common causes of death in males. Even if treatment is often of curative intent in early stages of the disease, up to 50% of patients relapse after primary therapy. Moreover, 10% to 15% of patients present in a primary metastatic stage of disease. In the past years the treatment landscape of metastatic castration-resistant prostate cancer expanded due to the development of second-generation antiandrogens (abiraterone acetate, enzalutamide), chemotherapeutic agents and radium-223. With the availability of several therapeutic lines, we are now confronted with the problem of choosing the most suitable therapy in each state of disease. As often observed in clinical routine, prostate specific antigen is not sufficient for early prediction of a therapy response. Furthermore, biomarkers for prediction of the optimal first-line therapy are badly needed in order to avoid primary resistance. Therefore, the present short review article gives an overview of currently available clinical and preclinical biomarkers for treatment response to metastatic castration-resistant prostate cancer therapeutic agents with the aim of providing support for a personalized decision-making process in everyday use.