As next generation stapling devices enter the marketplace with robotic adaptations, tri-staple technology, preloaded reinforcement materials, etc., in this perspective piece we assert that a “refresh” in our understanding of the mechanisms of action of these devices is needed. While much attention has been paid to explain the mechanical features of one device versus another, it seems that little to no attention is being paid to understand how an intestinal anastomosis responds biologically to the variations in their use and design. Here we will review various aspects of gastrointestinal stapling in the context of emerging technology in the field and expose the gaps in knowledge that exist regarding the effect of gastrointestinal stapling on the biology of healing.