Quality-of-life assessment tools for men with prostate cancer have given patients and health-care providers a nuanced understanding not only of how long patients will survive, but also how well they will live. Health-related quality of life (HRQOL) addresses the entire spectrum of human experience, including daily necessities, interpersonal relationships, physical and mental health, illness, and professional and personal happiness. Developing an HRQOL instrument is a methodologically rigorous process that requires fastidious attention to detail if the product is to be useful for patients and populations, and responsive to change over time. HRQOL instruments must be psychometrically sound, but also readily used by the target population. Instruments should ideally be administered by a neutral third party, to avoid bias of patients wanting to 'please' their physicians by masking underlying problems. The instruments used in HRQOL assessment can be general or specific to a particular disease process. General HRQOL domains assess overall well-being, typically with instruments that address general health perceptions, and social, emotional, and physical function. Disease-specific instruments might focus on how dysfunction in a particular organ or disease affects overall HRQOL. Several instruments specific to prostate cancer have been used on their own or in conjunction with more generic tools to assess HRQOL in men with prostate cancer.