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Introduction and Objectives: Renin-angiotensin-aldosterone system inhibitors (RAASi) are the cornerstone of treatment of heart failure with reduced ejection fraction (HFrEF). RAASi optimization in real-life care is challenged by hyperkalemia, a potentially fatal adverse event, which can necessitate downtitration or discontinuation of RAASi and negatively impact survival in HFrEF. The literature on this problem is sparse. We performed a systematic review of studies on HFrEF to investigate the prevalence, incidence, and risk factors of hyperkalemia, RAASi prescription rates, frequency of RAASi downtitration or discontinuation due to hyperkalemia, and the potential negative effect of the latter on prognosis., Methods: We conducted a MEDLINE (PubMed) search including observational and interventional studies published between January 1987 and May 2018., Results: A total of 30 observational and 18 interventional studies were included in the review. The incidence of hyperkalemia reported was between 0% and 63% in observational studies and was between 0% and 30% in clinical trials. Risk factors for hyperkalemia included RAASi prescription, older age, diabetes, and chronic kidney disease. In real-life studies, RAASi were downtitrated or discontinued in 3-22% of HFrEF patients; hyperkalemia was the reported cause in 5% of cases. No reports were found on the impact on prognosis of RAASi downtitration or discontinuation due to hyperkalemia., Conclusions: Hyperkalemia and RAASi downtitration or discontinuation are frequent, particularly in real-life HFrEF studies. Further research is needed to clarify the role of RAASi downtitration or discontinuation due to hyperkalemia and to assess its long-term prognostic impact in HFrEF patients., (Copyright © 2020 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)