Surprisingly perhaps for a tumor where there is such clear proof of a primary hormonal basis to its development, there is emerging evidence that all elements playing a key role in prostate cancer somehow affect the host immune system. This review turns the spotlight on some previously unsuspectable aspects, able to interact with the immune system in prostate cancer patients PSA, sex hormones, inflammatory infiltrates, cytokines, growth factors, neoformed blood vessels, neurotransmitters and neurotrophins, cigarette smoking, diet, therapeutic approaches. The concept of exploiting the immune system to combat cancer is not new, but only nowadays immunotherapy is a reality. Prostate cancer is an excellent target, involved in an increasing number of clinical immunotherapeutic trials. The main current purpose is to overcome the host immune tolerance of tumor cells. The most recent progresses in gene, monoclonal antibody and vaccine therapies are reported.