Availability of novel hormonal therapies as well as docetaxel and cabazitaxel treatment for metastatic castration?resistant prostate cancer (CRPC) has changed the outlook for this group of patients with improvements in progression?free survival and overall survival. Physicians often diagnose the progression of prostate cancer using serum prostate?speciifc antigen (PSA). However, serum PSA is not always correlated with the clinical status in CRPC. To evaluate the PSA dynamics with greater precision, understanding of the control of PSA and of the mechanisms of development of CRPC is needed. Moreover, it is necessary to use new hormonal therapies with an appropriate timing to optimally improve the prognosis and the QOL of the patients. In the present review, we ascertain the PSA dynamics and the mechanisms of the development of CRPC to assist in optimal utilization of the new treatments for mCRPC.