While the rising epidemic of obesity is primarily attributed to a sedentary lifestyle, poor dietary habits, and the aging of the population, secondary causes of obesity generally go undetected and untreated. These include endocrinological disorders, such as Cushing’s syndrome, polycystic ovary syndrome, hypothalamic obesity, hypogonadism, and hypothyroidism, as well as genetic, syndromic, and drug-related obesity. We present an overview of the major disorders associated with obesity, highlighting the pathophysiologic mechanisms and discussing the diagnostic and treatment strategies that are most helpful to practicing physicians in recognizing and treating these generally under-detected and undertreated disorders.