Despite excellent success rates with radical prostatectomy and radiotherapy for the treatment of prostate cancer, a significant number of patients will experience a rise in their serum prostate specific antigen (PSA) level. A variety of salvage options in this scenario have been investigated and the choice to pursue surveillance, single therapy or combination therapy depends on clinical assessment of risk and location of tumor recurrence. After radical prostatectomy, for example, patients with low risk local disease may not require secondary therapy or may benefit from salvage radiotherapy. Those with higher risk disease, based on PSA kinetics and tumor pathology may require systemic androgen deprivation therapy (ADT) with or without radiotherapy. Local recurrence after radiotherapy has the options of cryotherapy, brachytherapy or salvage surgery. ADT can also be applied in these patients at high risk of disease progression and cancer-specific mortality. Risk assessment in these settings is paramount as all secondary therapy options for prostate cancer have potential side effects that may significantly affect quality of life. We review the literature and discuss the current methods of risk assessment and the treatment options in prostate cancer once primary therapy fails.