Obesity is one of the leading causes of preventable death in the United States, second only to smoking. The annual number of deaths attributed to obesity is estimated to be as high as 400,000. Nearly 70% of the adult U.S. population is overweight or obese. The historical viewpoint toward obesity has deemed it to be a lifestyle choice or characterological flaw. However, given the emerging research into the development of obesity and its related complications, our perspective is changing. It is now clear that obesity is a heterogeneous disease with many different subtypes, which involves an interplay between genetic and environmental factors. The current epidemic of obesity is the result of an obesogenic environment (which includes energy-dense foods and a lack of physical activity) in individuals who have a genetic susceptibility for developing obesity. The pathophysiology associated with weight gain is much more complex than originally thought. The heterogeneous nature of the disease makes the development of treatment strategies for obesity difficult. Obesity in general is associated with increased all-cause mortality and cause-specific mortality (from cardiovascular, diabetic, hepatic, and neoplastic causes). Yet despite increased overall mortality rates, current evidence suggests that when these same patients are admitted to the intensive care unit (ICU), the obesity provides some protection against mortality. At present, there is no clear explanation for this obesity conundrum in critical illness.