At present, polyserositis (PS) remains a challenging entity, which resides both in the fact that there is confusion regarding the terminology, and that it is still understudied. We aimed to identify the etiologies of PS, reported in adult patients. Methods: We performed a systematic review of the literature on PubMed(MEDLINE) database, using the following (MESH) terms: pleurisy/etiology, pleural effusion/etiology, pericarditis/etiology, pericardial effusion/etiology, pericardial effusion chronic, ascites/etiology, ascitic fluid/etiology, polyserositis, serositis, and serositides. Results: A total of 1979 articles were identified, dating from 1973 onwards. After screening the articles, we included 114 patients from 23 articles (one case series including 92 patients and 22 case reports) in the final report. The most common diagnosis was neoplasia (30; 26.3%), followed by autoimmune diseases (19, 16.7%) and infections (16, 12.3%). Still, in 35 cases, the etiology of PS remained unkown. Conclusion: PS is a challenging and understudied entity, which is associated with a wide range of diagnoses. However, prospective studies should be developed in order to have a clear understanding regarding its etiologies and their prevalences.