Obesity has become an epidemic worldwide. It is accompanied by a multitude of medical complications including metabolic syndrome. Obesity may lead to fatty infiltration of multiple internal organs including liver, heart, kidney, and pancreas, causing organ dysfunctions. Fatty infiltration leads to chronic inflammation and tissue damage. Fatty infiltration in the liver results in nonalcoholic fatty liver disease, which is increasingly common nowadays. Recent studies in animals and humans indicate that obesity also is associated with fatty infiltration of gallbladder, resulting in cholecystosteatosis. The increased gallbladder lipids include free fatty acids, phospholipids, and triglycerides. Enhanced inflammation with an increased amount of fat in the gallbladder results in an abnormal wall structure and decreased contractility. In support of this notion, a recent experiment on the effect of Ezetimibe, which is a novel drug that inhibits intestinal fat absorption, on fatty gallbladder disease reveals that Ezetimibe can ameliorate cholecystosteatosis and restore in vivo gallbladder contractility. The proportion of cholecystectomies performed for chronic acalculous cholecystitis has increased significantly over the past two decades. An increase in gallbladder fat, which leads to poor gallbladder emptying and biliary symptoms, may partly explain this phenomenon. Although dietary carbohydrates have been demonstrated to be associated with fatty gallbladder disease, other potential modifiable environmental factors are not clear. The pathogenesis and prognosis of fatty gallbladder disease, including steatocholecystitis, and the relations of fatty gallbladder disease to nonalcoholic fatty liver disease, including steatohepatitis, and other components of metabolic syndrome are largely unknown. More research is needed to answer these questions.