In this systematic review, we studied different mechanisms explaining the obesity paradox in patients on maintenance hemodialysis, i.e., hemodynamic stability, the concentration of TNF-α receptors, neurohumoral response, role of inflammation, blood pressure, etc. also, the effect of age, gender, duration of treatment, acetyl-ghrelin on obesity paradox have been considered in our paper. This systematic review demonstrates the evidence of an inverse relationship between BMI and all-cause mortality in ESRD patients on maintenance hemodialysis. The gene discussed is GHRL; the disease is Obesity.