The gut incretin hormone, glucagon-like peptide 1 (GLP-1), regulates islet hormone secretion, circulating glucose levels, and body weight, making it an attractive agent for the treatment of type 2 diabetes. As cardiovascular disease represents the leading cause of death in patients with diabetes, it is important to understand how GLP-1-based drugs impact the cardiovascular system. Here, we review recent advances in our understanding of two incretin-based drug classes, GLP-1 receptor agonists and dipeptidyl peptidase 4 inhibitors, specifically in the context of heart failure. In addition to illustrating how these therapies influence cardiac signaling processes, we describe the cardioprotective mechanisms identified in preclinical studies, while reviewing the clinical data from studies in patients with type 2 diabetes. We end by speculating why observations made in preclinical studies are not necessarily reflected in a clinically relevant patient population.