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Objective: The 5alpha-reductase inhibitors (5ARIs) represent a valid therapeutic option in the long-term treatment of benign prostatic hyperplasia (BPH). One of the most debated topics is the interpretation of the variation of the serum PSA during treatment with 5ARIs. The objective of this review was to analyze the change in serum PSA levels over time and to evaluate its sensitivity and specificity in the screening for prostate cancer (CaP) during treatment., Methods: An extensive search using PubMed and Scopus was performed including the following key words: "5ARI", "finasteride", "dutasteride", "prostate cancer", "benign prostatic hyperplasia", "PSA", "kinetics", "PSA derivatives"., Results: The reduction of serum PSA during treatment with 5ARIs can be observed up to 48 months after the beginning of the therapy. This category of drugs seems to improve the diagnostic performance of PSA in screening CaP. On the other hand, there is a reduction of the diagnosis of indolent cancers. Any increase in PSA from nadir should be considered suspicious for malignancy. However, if the choice of a biopsy depended only on an increase of the values of serum PSA, a variable percentage of potentially aggressive tumors could not be diagnosed. Therefore, it is important to consider in the clinical and diagnostic follow-up other factors such as digital rectal examination, age, family history of CaP and imaging techniques., Conclusions: 5-ARIs have a positive impact on the specificity of PSA but they must not be the only tool that can identify CaPs with poor prognosis.