© 2013 Springer Science+Business Media Dordrecht. All rights are reserved. Obesity is an emerging public health concern that has numerous secondary health consequences, including heart disease, high blood pressure, diabetes mellitus, osteoarthritis, and overall reduced quality of life. Historically, obesity has been viewed as increased body fat caused by overconsumption of food, combined with the sedentary lifestyle of modern society. Simply put, energy input exceeds energy output, creating an excess in fat mass. This viewpoint largely focuses on environmental and social factors in the obesity epidemic. However, it fails to take into account a growing body of evidence from several monogenetic human obesity disorders and mutant mouse and rat obesity models that indicate a profound role for genetic factors. Although most of these monogenetic human conditions are rare, it is clear that the study of their molecular and cellular etiology will offer insights into the mechanisms that regulate appetite and satiety. The objectives of this review are to discuss how mutations in genes required for the formation or function of the cilium result in obesity in human and mouse models and how the cilium may function to regulate appetite and satiation responses.