10–20% of the population in Europe carries gallbladder stone. Many gallstones are asymptomatic, but symptoms and severe complications occur in more than 40% of patients above the age of 40 years, necessitating laparoscopic cholecystectomy. The cholelithiasis prevalence is even higher in most Hispanic populations of Central and South America, and in American Hispanics with native American ancestry. Overall, gallstone disease represents a serious load for healthcare systems; annually, an estimated 700,000 and more than 190,000 cholecystectomies are done in the United States of America and Germany respectively. Also, the average of the prevalence was 4-12% in Middle Eastern countries. Purpose of review: to highlight the role of genetic and non genetic risk factors for gall stone formation. These highlights are extrapolated from recently published and well respected studies and systematic reviews. Conclusion: causes, mechanisms of cholelithiasis and its correlation with the pathogenesis of related diseases are discussed and reviewed