Since attenuation of the signaling of RAGE has been suggested as a beneficial approach for the treatment of obesity and its comorbidity and being that these isoforms of RAGE act as decoy receptors for RAGE, diminishing its signaling (Miranda et al., 2018), the present article reviewed the concept of targeting of esRAGE and sRAGE signaling as a beneficial approach for the treatment of obesity. The gene discussed is AGER; the disease is Obesity.