The gall stone formation (cholelithiasis) is well known global health problem since very early times. Various biochemical and patho-physiological factors have been reported to be associated with gall stone disease such as stasis of bile, obstruction in bile duct, infection in bile, obesity, oestrogen level, inflammation of gall bladder valve, defective function of liver and gall bladder, reduction in bile salt concentration, change in cholesterol and bilirubin concentration and various precipitating factors for stone formation. Risk factors of cholelithiasis include overweight, age (near or above 40 years), female-menopausal age and racism with risk history of cholelithasis as found more prevalent in Caucasians than in people of other races. A lack of melatonin could significantly contribute to gallbladder stones, as melatonin inhibits cholesterol secretion from the gallbladder to enhances the conversion of cholesterol to bile and is an antioxidant, capable of reducing oxidative stress to the gallbladder. Clinical researchers believe that gallstones may be caused by a combination of risk factors, including inherited body chemistry, body weight, gallbladder motility with cholesterol crystallization and dietary habits. Role of various metal ions e.g. copper, iron, calcium, phosphate, sodium and potassium were also found to be responsible for nucleation of gall stone and their settling in gall stone bladder in cholelithiasis patients.