After receiving local treatment, many patients will develop a biochemical recurrence (BCR) in the absence of detectable distant disease (cM0) and comprise a significant proportion (20.1%) of prostate cancer disease states. The natural history of patients with BCR ranges from those with indolent, nonprogressive, slow prostate-specific antigen (PSA)-only progression to those ultimately destined to develop metastases and progress to a cancer-specific death. Pathologic predictors of BCR, clinical progression, and cancer-specific mortality are well established in the literature, although multiple novel predictors are emerging, which are highlighted. Traditional imaging cannot reliably distinguish local versus distant microscopic metastasis at the PSA levels that have been shown to confer survival advantage for salvage radiation therapy. We review past and present imaging standards and discuss novel imaging modalities, which may improve staging and offer opportunity for novel salvage therapies, including salvage lymph node dissection and stereotactic beam radiation therapy. With an emphasis on BCR after radical prostatectomy, both curative and palliative treatments are reviewed. This review contains 7 figures, 6 tables and 73 references Key words: biochemical recurrence, clinically undetectable metastases, molecular imaging, monitoring treatment response, prostate cancer, radical prostatectomy, rising prostate-specific antigen, salvage lymph node dissection, salvage radiation