Immunotherapy has emerged as a viable therapeutic option for patients with prostate cancer. There are multiple potential strategies that use the immune system, including therapeutic cancer vaccines that are designed to stimulate immune cells to target antigens expressed by cancer cells. Sipuleucel-T is a vaccine currently approved for the treatment of minimally symptomatic metastatic prostate cancer, whereas the vaccine PSA-TRICOM and the immune-checkpoint inhibitor ipilimumab are in phase III testing. Although there are no short-term changes in disease progression or available biomarkers to assess response, these agents appear to improve survival. One hypothesis suggests that this apparent paradox can be explained by the growth-moderating effects of these treatments, which do not cause tumor size to diminish, but rather stall or slow their growth rate over time. For this reason, the use of immunotherapy earlier in the disease process is being investigated. Another approach is to block immune-regulatory mechanisms mediated by the molecules cytotoxic T lymphocyte antigen 4 and programmed cell death protein 1. Additional future strategies will combine immunotherapy with other standard therapies, potentially enhancing the latter's clinical impact and thereby improving both time to progression and overall survival due to the combined effects of both treatments. Prospective trials are currently evaluating these hypotheses and will ultimately serve to optimize immunotherapy in the treatment of prostate cancer.