Prostate inflammation can lead to an elevation in the serum PSA concentration and confound the use of PSA kinetics. This can have considerable clinical consequences, since these measurements form the basis for important clinical decisions. Thus, there has been investigation into ways to decrease the confounding from inflammation, including repeat PSA measurements after a period of observation or a course of empiric antibiotics. This article reviews the evidence about elevations in PSA due to prostatitis and describes the controversy over the optimal approach to reduce its confounding impact on prostate cancer screening.