Cholecystitis and gallstones affect a large segment of the population in developed nations, and a small proportion of affected individuals subsequently develop cancer of the gallbladder. However, little is known about the possible beneficial effects of physical activity. Accordingly, a systematic review examined the influence of both acute and chronic exercise on gallbladder motility, and relationships were examined between habitual physical activity, gallbladder disease, and gallbladder cancer. A search of Ovid/MEDLINE from 1996 to November 2014 yielded 67 articles relating to physical activity and gallbladder function or disease; 18 of these relevant to the objectives of the review were supplemented by 22 papers from personal files and other sources. Because of the limited volume of material, all were considered, although note was taken of the quality of activity measurement, care in excluding covariates, and experimental design (cross-sectional, case-control or randomized controlled trial). The impact of physical activity upon gallbladder function remains unclear; acute activity could augment emptying by stimulating cholecystokinin release, and one of two training experiments found a small increase in gallbladder motility. The largest and most recent cross-sectional and case-control trials show a reduced risk of gallbladder disease in active individuals. A small number of randomized controlled trials in humans and one animal study generally support these trends, although the number of cases of gallstones are too few for statistical significance. Three studies of gallbladder cancer also show a non-significant trend to benefit from physical activity. Although there remains a need for further research, regular physical activity seems likely to reduce the risk of both gallstones and gallbladder cancer. A substantial number of individuals must be persuaded to exercise in order to avoid one case of gallbladder disease, but the attempt appears warranted because of the other health benefits of regular physical activity.