Prostate cancer is the most common cancer in men from Western industrialized countries and a significant proportion of patients progress to advanced metastatic disease, for which currently no curative treatment exists. Therefore, new therapeutic approaches need to be considered. Prostate specific membrane antigen (PSMA) is an integral, non-shed type 2 membrane protein that is highly and specifically expressed on prostate epithelial cells and strongly upregulated in prostate cancer. PSMA is also present in the neovasculature of other solid tumors. These findings have spurred the development of PSMA-targeted therapies and first-generation products have entered clinical testing. The proposed strategies range from targeted toxins and radionuclides to immunotherapeutic agents. The present review provides an overview of these approaches.