Until very recently, docetaxel was the only approved agent in castration-resistant prostate cancer (CRPC) and other effective therapeutic options are urgently needed. In recent years, several new agents with promising activity and a favourable toxicity profile have been developed and clinically investigated in the fields of hormonal, cytotoxic, targeted and immune therapy. In particular, recent results from two large phase III trials of sipuleucel-T and cabazitaxel show that these two agents significantly prolong overall survival in CRPC. Indeed, sipuleucel-T has recently been approved by the US FDA for the treatment of CRPC. Many other pharmaceuticals, which are presented in this review, have been investigated recently or are being investigated in phase III trials and might prove to be effective in the future. Reviewed articles are discussed in light of the innovations in study design brought by the Prostate Cancer Clinical Trials Working Group (PCWG2), which updated the Prostate-Specific Antigen Working Group (PCWG1) guidelines, in order to allow better identification of potentially active drugs in clinical trials.