Objectives. The importance of Gram-positive microorganisms and atypical bacteria in chronic bacterial prostatitis (CBP) has recently been described. For this reason, this study analyzes the etiology of CBP, as well as the evolution of antibiotic resistance through a systematic review. Material and methods. A systematic review of studies obtained through the MEDLINE (PubMed) database, related to the etiology and antibiotic resistance profile of CBP, published up July 1, 2021. Results. The most frequent isolated microorganisms that we have found in publications are Enterococcus faecalis (46.90%), Staphylococcus spp. (22.30%), Escherichia coli (15.09%) and atypical bacteria (6.04%). Conclusions. CBP is undergoing and unprecedented change of paradigm. Gram-positive bacteria and atypical bacteria are the main pathogens involved in the aetiology of this entity. This forces us to rethink the therapeutic strategy used, since it is necessary to use antibiotics that assume the etiological change and the profile of antibiotic resistance described.