Since its discovery in 1979, serum PSA has revolutionized how physicians manage men with prostate cancer. PSA screening, although currently under much debate, has been recommended by most North American medical bodies, including the Canadian Urological Association, to be performed as a shared-decision making process after discussing with patients the pros and cons of treatment. Although most commonly thought of as a screening tool, serum PSA has also been used to predict tumor volume, stage and prognosis in patients before and after treatment. In this review, we examine PSA testing and its effectiveness in the diagnosis and management of prostate cancer. Further, we also evaluate recent literature regarding the use of PSA derivatives and other prostate cancer markers, such as proPSA, bPSA, and hk2