Mucosal injury and inflammation are cardinal manifestations of inflammatory bowel diseases (IBD), arising when the effects of cytotoxic factors and conditions overwhelm the cell's capacity for defense (i.e. cytoprotection) or repair. To date, most research in this area has focused primarily on agents and processes involved in producing tissue injury, with less consideration given to inherent mechanisms of cytoprotection and cellular repair. Therapeutic approaches to IBD reflect this bias, being largely directed towards down-regulating the inflammatory process by inhibiting the production of immune and inflammatory mediators. This review will focus on the cell's inherent ability to defend itself against cellular stress and injury through the production of evolutionarily conserved stress proteins called heat shock proteins (HSP). The physiological role of these proteins in maintaining intestinal epithelial cell structure and function will be reviewed, with emphasis on studies that examine the role of HSP in IBD. A clearer understanding of the innate cytoprotective mechanisms inherent in intestinal epithelial cells will foster the development of new insights into basic epithelial cell biology, which ultimately can be used to establish target-specific therapies directed at reducing or alleviating mucosal injury, thereby promoting tissue healing and repair.