CD44 has been identified as one of the adhesion molecules that regulate cell migration in inflamed tissue. The principal ligand of CD44 is hyaluronan, and CD44 is involved in the metabolism of this compound. Furthermore, an increasing quantity of evidence suggests that CD44 has various functions related to inflammatory disease. This review focuses on the potential roles of CD44 in the pathogenesis of chemical-induced liver injury and discusses some of the functions of this protein in pathological processes. The discovery that CD44 deficiency induces severe liver injury, (associated with an increase in hepatocyte apoptosis) rather than suppressing liver inflammation is summarized. These data suggest that targeted therapies against adhesion molecules should be monitored carefully to ensure that liver disease is not exacerbated by treatment.