Heart failure and diabetes are two most frequent conditions in the modern times that interact with each other. Comorbidity of heart failure and diabetes is clinically common, posing new challenges to the safety of clinical medication. This paper provides a systematical review of the status quo of research on the comorbidity in the aspects of epidemiology, clinical symptoms and risk of prognosis, physiological and pathological mechanism, and drug selection, focusing on the safety and effectiveness of using drugs for heart failure and diabetes for patients with the comorbidity, to provide guidance for decision making in clinical medication.