The prostate-specific membrane antigen (PSMA) has received increased consideration during the past few years as an excellent target for both imaging and therapy of prostate cancer. After many years of outstanding preclinical research, the first significant step forward in clinical use was achieved in 2008 with the first human experience with the small-molecule PSMA inhibitors I-MIP-1972 and I-MIP-1095. A clinical breakthrough followed in 2011 with Ga-PSMA-11 for PET imaging and I-MIP-1095 for endoradiotherapy of metastatic prostate cancer. Since then, PET/CT with Ga-PSMA-11 has rapidly spread worldwide, and endoradiotherapy with PSMA ligands has been conducted at increasing numbers of centers. Ga-PSMA-11 is currently the subject of multicenter studies in different countries. Since 2013, I-related PSMA therapy has been replaced by Lu-labeled ligands, such as PSMA-617, which is also the subject of multicenter studies. Alternative PSMA ligands for both imaging and therapy are available. Among them is Tc-MIP-1404, which has recently entered a phase 3 clinical trial. This article focuses on the highlights of the development and clinical application of PSMA ligands.