The physician’s primary responsibility in caring for a prostate cancer patient is to address the patient’s concerns regarding treatment and prognosis. Fortunately, the prognosis for prostate cancer, particularly for localized disease, is often favorable. Given that most patients will have survival measured in years, prostate cancer can reasonably be characterized as a “chronic” disease of aging (1). As with most chronic diseases, health-related quality of life (HRQOL) becomes a primary concern for the patient, and an appreciation of HRQOL outcomes plays a role in treatment decision making. The use of HRQOL as an endpoint for treatment has been increasingly emphasized in urologic and oncologic clinical trials as a means to differentiate between various therapies and to track disease progression (2–6). This chapter introduces state of the art concepts underlying the assessment of HRQOL, gives guidelines for selecting HRQOL instruments, and summarizes the contemporary literature related to prostate cancer HRQOL.