Gallbladder cancer is a relatively rare neoplasm that shows, however, high incidence rates in certain world populations. The interplay of genetic susceptibility, lifestyle factors and infections in gallbladder carcinogenesis is still poorly understood. Age-adjusted rates were calculated by cancer registry-based data. Epidemiological studies on gallbladder cancer were selected through searches of literature, and relative risks were abstracted for major risk factors. The highest gallbladder cancer incidence rates worldwide were reported for women in Delhi, India (21.5/100,000), South Karachi, Pakistan (13.8/100,000) and Quito, Ecuador (12.9/100,000). High incidence was found in Korea and Japan and some central and eastern European countries. Female-to-male incidence ratios were generally around 3, but ranged from 1 in Far East Asia to over 5 in Spain and Colombia. History of gallstones was the strongest risk factor for gallbladder cancer, with a pooled relative risk (RR) of 4.9 [95% confidence interval (CI): 3.3-7.4]. Consistent associations were also present with obesity, multiparity and chronic infections like Salmonella typhi and S. paratyphi [pooled RR 4.8 (95% CI: 1.4-17.3)] and Helicobacter bilis and H. pylori [pooled RR 4.3 (95% CI: 2.1-8.8)]. Differences in incidence ratios point to variations in gallbladder cancer aetiology in different populations. Diagnosis of gallstones and removal of gallbladder currently represent the keystone to gallbladder cancer prevention, but interventions able to prevent obesity, cholecystitis and gallstone formation should be assessed.