The aim of this review is to critically analyze the current state of research in selected biomarkers and genomic-based tests for prostate cancer (PCa) diagnosis, staging, prognostication, and monitoring. Although in Western societies, PCa is the most common solid malignancy and the second leading cause of cancer death in men, the vast majority of men with PCa are diagnosed with clinically localized disease. The widespread use of prostate-specific antigen (PSA) testing, on one hand, has resulted in earlier PCa detection at a potentially more curable stage, but on the other hand has led to an increase in the rate of negative biopsies, as well as overdetection and overtreatment of potentially indolent tumors that would not have become life-threatening to a patient. A multitude of molecular tests and algorithms has been developed to enhance diagnostic accuracy, improve pretreatment and post-treatment patient risk stratification, and identify aggressive versus indolent disease to facilitate therapeutic decision-making. PSA and derivatives (PSA kinetics, PSA density, percentage of free PSA) as well as algorithms based on PSA and PSA isoforms measurements (prostate health index, four-kallikrein score), urinary molecular biomarkers-based tests (Prostate Cancer Antigen 3, and the Michigan Health System Prostate Score) and selected genomic/proteomic tests now commercially available for disease prognostication (such as Confirm MDx, Prostate Core Mitomic Test, Oncotype DX, Prolaris, ProMark, and Decipher) are herein discussed to inform the readers about current and future clinical applications and their limitations. Finally, we briefly touch upon potential biomarkers predictive of response to therapy, such as androgen receptor splice variant AR-V7, and detection and quantification of circulating tumor cells in the blood stream.