O besity is arguably the world’s most prevalent nutritional disorder and is a substantial contributor to morbidity and early mortality. Obesity is known to have a strong genetic component, but the specific influential genes in humans are largely unknown. A new paper describes a genetic variant that appears as though it may cause some people to be fatter or thinner than others (see the related article beginning on page 1762). This commentary considers the strength of the evidence in support of this finding and discusses additional research questions that should be addressed in further evaluations of this genetic variant as a putative contributor to human obesity.