The options available for patients with recurrent prostate cancer are limited. Men who have failed external-beam irradiation as the primary treatment are rarely considered for potentially curative salvage therapy. Traditionally, only palliative treatments have been offered with hormonal intervention or simple observation. A significant percentage of these patients have only locally recurrent cancer and are thus candidates for curative salvage therapy. Permanent brachytherapy with iodine-125 or palladium-103 has been used in an attempt to eradicate the remaining prostate cancer and prevent the need for additional intervention. It is critical in this population to identify patients most likely to have distant metastases or who are unlikely to suffer death or morbidity from their recurrence, in order to avoid potential treatment morbidity in those unlikely to benefit from any intervention. Following salvage brachytherapy, up to 98% of these cancers may be locally controlled, and 5-year freedom from second relapse is approximately 50%. With careful case selection, relapse-free rates up to 83% may be achieved. A schema is presented, suggesting that it may be possible to identify the patients most likely to benefit from salvage treatment based on prostate-specific antigen (PSA) kinetics and other features. Such features include histologically confirmed local recurrence, clinical and radiologic evidence of no distant disease, adequate urinary function, age, and overall health indicative of at least a 5- to 10-year life expectancy, prolonged disease-free interval (> 2 years), slow PSA doubling time, Gleason sum < or = 6, and PSA < 10 ng/mL.