Transmural defects of the gastrointestinal tract can be classified into three distinct entities that include leaks, perforations, and fistulae. Each arise from different mechanisms and are managed accordingly. Leaks occur most often following surgery, while perforations occur most often following flexible endoscopic maneuvers. Fistula arise from a variety of mechanisms, such as an evolution from surgical leaks as well as from specific disease states. Endoscopic management plays a vital role in the treatment of transmural defects as long as the region of interest can be accessed with the appropriate endoscopic accessories.