In the past 5 years much progress has been made in understanding the molecular basis of Crohn's disease, a multifactorial chronic inflammatory disease of the gastrointestinal tract. Data suggest that hampered autophagy—the major lysosomal pathway for recycling of cytoplasmic material—might contribute to an increased susceptibility to Crohn's disease. Consequently, intense investigations have started to evaluate the potential value of autophagy as a therapeutic target and as a highly needed diagnostic tool. Interestingly, as well as the promising introduction of direct autophagic modulators, several drugs already used in the treatment of Crohn's disease might exert at least part of their effect through the regulation of autophagy. However, whether this phenomenon contributes to or rather counteracts their therapeutic use, remains to be determined and might prove to be highly compound-specific. Here we review the complex and emerging role of autophagy modulation in the battle against Crohn's disease. Moreover, we discuss the potential benefits and deleterious effects of autophagic regulation by both new and clinically used drugs.