Prostate cancer continues to be the most common cancer and second leading cause of cancer-related death among men. The use of markers, particularly serum-based prostate specific antigen (PSA), has contributed to the rapid rise in diagnosed cases in the late 1980s and early 1990s, but new diagnostic and possible therapeutic markers are needed and are currently being evaluated. One of these, prostate-specific membrane antigen (PSMA), is an approximately 100-kDa type II transmembrane protein originally thought to be highly selectively expressed in all types of prostatic tissue, with expression being upregulated in androgen-depleted or androgen-independent states. The radioimmunoconjugate form of the anti-PSMA monoclonal antibody (mAb) 7E11 is currently being used to diagnose prostate cancer metastasis and recurrence. In addition, Phase I and II trials have started utilizing PSMA in different therapeutic ways, with promising results. Recent exciting work has demonstrated PSMA expression in endothelial cells of vessels restricted to the tumor-associated neovasculature. This finding expands the possible beneficial uses of PSMA, as new anti-PSMA mAbs continue to be developed.