Colon capsule endoscopy (CCE) is a minimally invasive technique specifically designed to explore the colon without sedation and air insufflation. CCE may overcome some of the limitations of colonoscopy. Second-generation CCE (CCE-2) was proved accurate in detecting colonic neoplastic lesions when used in average-risk individuals. The evidence to date supports the use of CCE-2 in cases of colonoscopy failure, in patients unwilling to undergo colonoscopy, and when colonoscopy is contraindicated. Other potential applications, such as colorectal cancer screening or diagnostic surveillance of inflammatory bowel disease, require clarification.