Individuals with spinal cord injury (SCI) face a disproportionate burden of obesity and cardiometabolic disease, however, evidence to guide pharmacologic treatment is minimal. Mainstay diet and exercise recommendations often yield modest, unsustainable results for those with SCI. In the general population, glucagon-like peptide-1 receptor agonists and dual agonists (GLP-1s) have emerged as potent therapies for obesity and related cardiometabolic disorders. Initially developed for type 2 diabetes mellitus, GLP-1s improve glycemic control, promote substantial weight loss, and reduce other cardiometabolic risk factors. Although robust data from the general population show weight-dependent and independent benefits, evidence specific to SCI is limited to case presentations. These reports suggest the potential for significant reductions in body fat and improvements in cardiometabolic risk. However, concerns remain regarding potential complications, including worsened gastrointestinal dysfunction, reduced muscle mass with a proclivity to develop pressure injuries, and further compromises in bone density. This special communication draws on evidence from the general population and limited SCI-specific evidence to examine the relevance of GLP-1s for individuals with SCI and provides commentary on key clinical considerations for navigating their use in this population.