Starting from the discovery that several rare forms of obesity, called monogenic obesity, result from a mutation in single genes primarily located in the leptin–melanocortin pathway [15,16], recent evidence has identified additional selected genes associated with obesity, providing that the genetic background can play a pivotal role in causing or triggering susceptibility to the pathology when associated with environmental factors such as overeating and PE reduction [17,18]. The gene discussed is LEP; the disease is obesity disorder.