The US FDA recently approved sipuleucel-T (Provenge(®), Dendreon, Inc., WA, USA) on the grounds of the results reported by a Phase III trial, which are presented and discussed in detail in this article. This study was conducted in 512 metastatic castration-resistant prostate cancer patients randomized in a 2:1 ratio to receive either active therapy or placebo. Although no difference in time to progression was observed, a survival advantage was achieved, with a statistically meaningful 4.1-month improvement in median survival in the active arm with respect to the placebo arm (25.8 vs 21.7 months). In view of its favorable toxicity profile and manageable route of administration, sipuleucel-T is the ideal agent to be combined with other standard treatments, which include hormonal, cytotoxic and biological agents, and radiotherapy. Sipuleucel-T opens exciting new paradigms for prostate cancer and increases the possibility of survival prolongation for men with this deadly disease.