Since the advent of colon capsule endoscopy (CCE) in 2006, several papers have addressed its potential role in evaluating colonic mucosa in a painless and patient-friendly way. We selected some landmark studies and relevant meta-analyses for each main clinical scenario in which CCE is currently used. These papers were briefly summarized with emphasis on their strengths and limitations. We focused on papers comparing CCE to conventional colonoscopy, on those targeting screening patients, on those evaluating CCE for completing incomplete colonoscopies (involving both CCE and computed tomography colonography (CTC)), and finally on those testing CCE in patients with inflammatory bowel diseases. Rather than being an exhaustive and conclusive systematic analysis, the present paper is intended to critically appraise the role of CCE, moving from the most relevant clinical studies conducted with accurate methodology and large sample size.