The pathogenesis of inflammatory bowel disease (IBD) is multifactorial and results from an interaction between genetic, immunologic, microbial, and environmental factors. Certain drugs could act as a trigger for the disease and have been implicated in the development of new onset IBD in a number a studies. These relationships are based on case reports and cohort studies, as proving this in the context of randomized controlled trials would be difficult. Drugs that have been linked to causing or worsening IBD include isotretinoin, antibiotics, nonsteroidal antiinflammatory drugs, oral contraceptives, mycophenolate mofetil, etanercept, ipilimumab, and rituximab. Bowel preparation for colonoscopy has also been associated with aphthoid lesions that may be confused with IBD. However, given the source of these reports we have to be cautious in the interpretation of the data before concluding that these drugs trigger IBD and what is being observed is not related to other confounding factors. Different pathogenic mechanisms have been suggested for the different drugs listed above. In order to clarify the confusion a comprehensive literature review was performed with the goal of advancing the knowledge on this subject.