Prostate cancer remains the second leading cause of cancer death in men in the USA and most western countries. Prostatic acinar adenocarcinoma is the most commonly diagnosed form of prostate cancer. Small-cell neuroendocrine carcinoma is less frequently identified at the time of initial diagnosis, but this highly aggressive form of prostate cancer is increasingly observed in patients who have failed first- and second-line hormone therapy. Thus, developing and exploring models of neuroendocrine prostate cancer (NePC) are of increasing importance. This review examines the relevant xenograft tumor and genetically engineered mouse models of NePC, with the aim of addressing salient features and clinical relevance.