Prostate cancer (PCa) is fifth leading cause of cancer-associated deaths in men worldwide. Although the application of the serum prostate-specific antigen (PSA) screening test resulted in an increase in the PCa diagnosed cases, it demonstrated a negligible benefit regarding the associated mortality. Treatment options vary, with active surveillance to be preferable for patients with low-risk PCa and therapy of advanced castration-resistant PCa to rely on α-emitters and cytotoxic chemotherapy. Although recent developments have led to the approval of novel drugs for the treatment of castration-resistant PCa, the optimal sequence and timing of medication have not been yet determined. New screening modalities could improve the discriminatory accuracy between tumors with favorable clinical prognosis. Implementation of proteomic-based biomarkers appears to be a promising improvement, which could enable a more accurate diagnosis, guide treatment and improve patient outcome. Reviewed here are urinary proteome-based approaches for detection of PCa and patient management.