An asymptomatic rising serum prostate-specific antigen (PSA) level is the most common form of failure after radical radiotherapy for localized prostate cancer, but there is no consensus as to how it should be managed. This review addresses the following three questions concerning men with PSA failure after radiotherapy: (i) what is the course of the disease without further intervention?; (ii) what is the role of radical treatment, such as salvage prostatectomy?; and (iii) should androgen deprivation be started immediately or should it be delayed until clinical progression occurs? An algorithm for the management of PSA failure after radical radiotherapy for localized prostate cancer is proposed.