Diabetes mellitus (DM) is associated with a specific cardiac phenotype characterized by structural and functional alterations. This so-called diabetic cardiomyopathy (DM CM) is clinically relevant as patients with DM show high incidence of heart failure. Mechanistically, several parameters interact on the cardiomyocyte level leading to increased inflammation, apoptosis, reactive oxygen species and altered calcium signaling. This in turn provokes functional myocardial changes that might inter alia play into the worsened clinical outcome in DM patients. Therefore, efficient therapeutic options are urgently needed. This review focuses on mechanistic effects of currently recommended antidiabetic treatment and heart failure therapy for DM CM.