Accurate prognostication is a prerequisite for accurate therapeutics and management of prostate cancer because indolent tumors may require no intervention, whereas aggressive tumors lead to patient mortality. There is a critical need to define these subgroups of patients with prostate cancer differing in clinical outcome. Prognostic nomograms based on clinical data provide useful predictions of clinical states and outcomes, but they need further refinements to improve accuracy and universality. Genomic and proteomic analyses have provided many novel markers that may help define prognostic parameters based on the underlying biology of prostate cancer progression at the molecular level. These molecular markers are likely to augment traditional prognostic modalities by providing a set of molecularly defined and quantifiable variables. Encompassing the genome, transcriptome, and proteome of prostate cancer will likely provide "molecular signatures" that will bridge prognostication, prediction, and treatment in a single continuum.