While colonoscopy is the gold standard for the evaluation of the colon, research on post-colonoscopy colorectal cancers has increased our awareness of its limitations. In this issue of the Journal, Erichsen et al. provide evidence to suggest that post-colonoscopy colorectal cancers are most likely due to missed cancers at the time of the index colonoscopy, rather than due to aggressive tumor biology. Ultimately, studies demonstrating the shortcomings of colonoscopy are a call to action for the gastroenterology community to develop strategies and new technologies to improve the effectiveness of colonoscopy.