Gastrointestinal healing is a topic rarely reviewed in the literature, yet it is of paramount importance to the surgeon. Failure of anastomotic healing may lead to life‐threatening complications, additional surgical procedures, increased length of stay, increased cost, long‐term disability, and reduced quality of life for the patient. The goal of this article is to review the biological response to wounded tissue, to outline discrete differences between skin and gastrointestinal healing, to discuss local and systemic factors important to gastrointestinal healing, and to compare methods of measuring collagen content and strength of the newly formed anastomosis. Part II of this review will focus on techniques and therapies available to optimize anastomotic healing. © 2006 Wiley‐Liss, Inc. Microsurgery, 2006.