Patients whose only sign of recurrence after local therapy for prostate cancer is a rising prostate-specific antigen level (PSA-only recurrence) have become more common. We have developed two models to predict PSA-only recurrence after radical prostatectomy, one using traditional factors (race, sigmoidal transformation of PSA, postoperative Gleason sum, and organ confinement) and a second using traditional clinical and pathologic variables combined with molecular biomarker levels. Treatment options for patients with PSA-only recurrence include observation, radiation therapy for patients who have undergone surgery, salvage surgery or cryotherapy for patients who have received radiotherapy, and traditional or nontraditional hormonal therapy. Radiation for PSA-only recurrence is likely to benefit men who have no adverse pathology, a low PSA level at recurrence, and PSA recurrence after the first year. Salvage radical prostatectomy and cryotherapy pose a relatively high risk of incontinence and other morbidity and should be reserved for carefully selected patients with a high likelihood of organ-confined disease. Hormonal therapy is probably the single most beneficial treatment for PSA-only recurrence. Nontraditional low-dose oral hormonal therapy and intermittent hormonal therapy are gaining in popularity, although their long-term efficacy is unknown. More clinical trials are needed to fine-tune prognostic models and to determine the best treatments, alone or in combination, for PSA-only recurrence.