Clinically relevant outcomes such as distant metastases and death from prostate cancer do not occur for many years after definitive treatment for localized prostate cancer. In view of the long natural history of prostate cancer, the identification and validation of surrogate endpoints that can be measured earlier and correlate with clinical progression or survival are of great utility in clinical cancer research. With the introduction of prostate-specific antigen (PSA) as a marker in the mid-1980s, PSA has become an important tool for monitoring disease progression following definitve treatment of localized prostate cancer and the concept of “biochemical” recurrence, an event that precedes clinical recurrence by many years, has been developed. Biochemical failure has become widely accepted to evaluate the effectiveness of definitive local therapies and is used for both research and clinical purposes. Biochemical recurrence has been investigated as a prognostic factor and as a potential surrogate endpoint in different stages of disease; however, on the basis of conflicting results from previous studies, a consensus on the ability of biochemical failure to act as a reliable surrogate endpoint for clinical progression and survival has not yet been reached.