We review the role of immunotherapy in castration resistant prostate cancer. Two immunotherapeutic strategies have been applied, isolated or in combination, either with each other or with other agents with demonstrated efficacy in this scenario that would play a role as immunomodulators: vaccines or monoclonal antibodies aimed to block immune response checkpoint inhibitors. Although CRPC presents, a priori, characteristics suggesting that immunotherapy may play a relevant role as a therapeutic strategy, its clinical application has demonstrated a limited and heterogeneous activity, in terms of proportion of responders and response intensity. Generally, the objective response rate is very low, although, in patients who have response it is possible to detect a clear, long-lasting benefit. Only the autologous vaccine Sipuleucel T has demonstrated an overall survival increase in patients with good prognosis criteria. In these treatments, it is characteristic that no progression free survival increase is visible due to its action mechanism. PSA evolution may not be considered a surrogate variable of radiological response or clinical benefit in this environment either. It is necessary to identify what patient's or tumor's characteristics are able to maximize the response. An important limitation is the absence of response predictive biomarkers that serve for patient preselection. As a general rule, the best responses with isolated immunotherapeutic treatments have been observed in patients with low tumor load, which may suggest that their optimal application could be in earlier phases of the disease (high risk localized, biochemical failure, etc) Combination strategy, without doubt the one with best future, is based on additional treatments increasing cell lysis with the subsequent antigen exposure and/ or producing an immunomodulatory effect that can surmount tumor induced immunologic tolerance. The results obtained suggest that immunotherapy may be more effective in combined therapy with other active therapies (abiraterone, enzalutamide, Radium 223, docetaxel) in a fight to achieve disease chronification.