The optimal management of patients with an elevated post-prostatectomy prostate-specific antigen (PSA) level remains to be determined. In the pre-PSA era, many patients received immediate adjuvant radiation therapy on the basis of adverse pathologic features following prostatectomy. However, since the advent of postoperative PSA monitoring, the PSA level has become the most specific measure for determining the presence of residual disease. An elevated postoperative PSA in correlation with other factors, such as pathologic stage and imaging studies, can be a specific marker of local recurrence in most patients. Through careful case selection, treatment design, and dose delivery, up to 80% of patients can achieve a complete response (PSA < 0.1 ng/mL) following postoperative therapeutic irradiation for an elevated PSA. This treatment can be delivered with minimal toxicity to the rectum and minimal risk of increasing incontinence. Pending the results of randomized trials, an appropriate therapeutic option for high-risk patients following prostatectomy would be to wait for an elevated PSA and then proceed with a course of potentially curative radiotherapy.