Biochemically recurrent prostate cancer is an increasingly common disease state, with more than 25,000 cases occurring annually in the United States. Fortunately, progress continues to be made to more effectively identify metastatic disease, optimize existing therapies, and develop new technologies and therapeutic strategies for the timing and delivery of systemic treatments to improve outcomes. This review covers three topics related to the diagnosis and treatment of men with biochemical recurrence (BCR). First, we provide an update on the state of the rapidly evolving field of molecular imaging and its place in practice. Second, we describe validated clinicopathologic methods to risk stratify patients with biochemically recurrent disease, including new gene expression classifiers, to personalize postoperative radiotherapy (RT) timing. Last, we define our approach to optimal management with systemic therapy, including identifying the patients who may benefit most and balancing the duration and timing of treatment with consideration of the effect of therapy on quality of life (QOL) and medical complications associated with treatment.