Surgery, and radiation therapy remain the standard treatments for newly diagnosed prostate cancer patients. Nonetheless, these aggressive treatments are associated with decreased quality of life with altered sexual and urinary functions. Using modern risk stratification, several centers have gained significant experience in identifying patients with a low risk of prostate cancer progression and have adopted an active surveillance program with delayed, selective, or curative therapy. Interestingly, only limited numbers of patients under active surveillance require additional treatment. Recent data suggest that delayed treatment does not appear to alter the clinical outcome among those highly selected patients. A better understanding of the molecular determinants of prostate cancer behavior would not only enable healthcare professionals to identify which cases need aggressive treatment but, perhaps more importantly, would also indicate potential targets for the development of novel therapeutic strategies.