It is clear that the cause of obesity is a result of eating more than you burn. It is physics. What is more complex to answer is why some people eat more than others? Differences in our genetic make-up mean some of us are more driven towards food and so eat more than others. We now know that the genetics of body-weight, on which obesity sits on one end of the spectrum, is in actuality the genetics of how our brain controls appetite. In this talk, I will discuss the ‘fat-sensing’ melanocortin pathway, as well as our efforts to map the feeding circuitry in the human brain. In contrast to the prevailing view, body-weight is not a choice. People who are obese are not bad or lazy; rather, they are fighting their biology.