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ABSTRACT Introduction Neuroendocrine prostate cancer (NEPC) is an aggressive form of prostate cancer frequently seen after prolonged treatment of castration resistant prostate cancer (CRPC). NEPC has become increasingly prevalent over the last 20 years, with a poor prognosis caused by a late diagnosis and limited treatment options. Recent advances in PET/CT imaging and targeted radioimmunotherapy are promising, but more research into additional treatment options is needed. Areas covered The aim of this review is to analyze the current imaging and treatment options for NEPC, and to highlight future potential treatment strategies. A Pubmed search for ‘Neuroendocrine Prostate Cancer’ was performed and relevant articles were reviewed. Expert opinion The recent FDA approval and success of 177 PSMA Lutetium in CRPC is promising, as 177 Lutetium could potentially be paired with a NEPC specific biomarker for targeted therapy. Recent laboratory studies pairing DLL3, which is overexpressed in NEPC, with 177 Lutetium and new PET agents have showed good efficacy in identifying and treating NEPC. The success of future development of NEPC therapies may depend on the availability of 177 Lutetium, as current supplies are limited. Further research into additional imaging and treatment options for NEPC is warranted. Plain Language Summary Neuroendocrine prostate cancer (NEPC) is a rare form of prostate cancer. People with NEPC have typically had previous treatment for prostate cancer. NEPC is usually found after prostate cancer cells have spread outside of the prostate. NEPC may not produce typical prostate cancer markers such as prostate specific antigen (PSA). This can make detection of NEPC difficult. NEPC is difficult to treat because NEPC does not respond very well to typical prostate cancer medications. Because of this, people with NEPC typically have a shortened survival. Many researchers have been developing new ways to find and treat NEPC. New methods of imaging with PET/CT scans are better at detecting NEPC than standard imaging. Treatments that specifically target NEPC cells are currently being researched, but these treatments have not been used on any patients yet. This article describes these research efforts and recommends that more research should be done to find treatments for NEPC.