Current dilemmas for physicians managing patients with localized prostate cancer include deciding: (1) which patients need aggressive treatment; (2) what treatment options are best for a given patient; and (3) what treatment outcomes can be expected. This article reviews our ability to prognosticate outcome (including pathological stage and disease-free survival rate) in patients with clinically localized adenocarcinoma of the prostate (AJCC, stage T1-T2. N0, M0) subsequent to analysis of several contemporary series involving patients treated with radical prostatectomy and external-beam radiation therapy. Pretherapy prostate-specific antigen (PSA) level (< or =4 ng/mL or >20 ng/mL) and Gleason score (< or =4 or > or =8) as individual variables provide independent prognostic information for only a subset of patients undergoing radical prostatectomy and external-beam radiation therapy. Pathological stage is the most powerful predictor of outcome following radical prostatectomy, and its prediction (organ-confined vs. seminal vesicle or lymph node involvement) is aided by knowledge of clinical stage, Gleason score, and PSA level. Planned systematic biopsies also provide useful prognostic information for the prediction of pathological stage and tumor volume, as well as providing additional tissue for pathological assessment of tumor heterogeneity. Several novel markers of biological aggressiveness are associated with critical steps of the metastatic cascade (growth, invasion, angiogenesis, and resistance to apoptosis) and include the p53 tumor suppressor gene, the bcl-2 proto-oncogene, markers of increased proliferation (Ki-67), apoptosis, and angiogenesis (microvessel density). Their evaluation in clinical specimens is currently being used to prognosticate outcome. Current clinical and pathological parameters provide a "ballpark" estimate of outcome for patients with clinically localized prostate cancer. Further elucidation of the critical molecular events associated with prostate cancer progression and metastasis should help in identifying molecular markers that more accurately predict the prognosis for an individual patient with clinically localized prostate cancer.