The trend toward decriminalization of cannabis (marijuana) continues sweeping across the United States. Colorado has been a leader of legalization of medical and recreational cannabis use. The growing public interest in the medicinal properties of cannabis and its use by patients with a variety of illnesses including inflammatory bowel disease (IBD) makes it important for pediatric gastroenterologists to understand this movement and its potential effect on patients. This article describes the path to legalization and “medicalization” of cannabis in Colorado and the public perception of safety despite the known adverse health effects of use. We delineate the mammalian endocannabinoid system and our experience of caring for children and adolescents with IBD in an environment of increasing awareness and acceptance of its use. We then summarize the rationale for considering that cannabis may have beneficial and harmful effects for patients with IBD. Finally, we highlight the challenges federal laws impose on conducting research on cannabis in IBD. The intent of this article is to inform health care providers about the issues around cannabis use and research in adolescents and young adults with IBD.