Table 1 summarizes current knowledge derived from in vitro, in vivo, and human studies regarding the emerging therapeutic effects of β3-adrenergic receptor agonists, incretin hormones, glucagon, their related pharmacological mimetics, and GLP-1-based multi-agonists, as new treatment options for enhancing thermogenesis and combat obesity. The gene discussed is GCG; the disease is obesity due to melanocortin 4 receptor deficiency.