Diabetes mellitus (DM) is frequent among heart failure (HF) patients with a further projected increase in prevalence in next years. DM promotes the development of both HF with reduced (HFrEF) and preserved ejection fraction (HFpEF) through different mechanisms. As the general prevalence of both DM and HF is growing worldwide, it is important to define the pathophysiologic mechanisms driving the development of HF in DM patients. These include changes in the cardiac metabolism, mitochondrial dysfunction, impairment in insulin signaling, maladaptive inflammation, coronary microvascular dysfunction, endoplasmic reticulum stress, autophagy suppression, and structural changes, among the main ones. In recent years, novel glucose-lowering treatments, especially sodium-glucose cotransporter 2 inhibitors (SGLT-2is), have shown a strikingly positive impact on the natural history of HF. This has led to a progressive change in choosing SGLT-2is in DM patients at high risk for cardiovascular disease, supported by recent guidelines. The knowledge about novel pathophysiological mechanisms linking DM and HF may open the way to the development of new targeted therapies in the future. In this review, we will summarize general aspects dealing with incidence, prevalence, and pathophysiology of DM in HF patients. As well, we discuss the therapeutic targets to reduce the disease burden and the current evidence of glucose-lowering drugs in patients with DM and HF.