The pathogenesis of endometriosis remains poorly defined. The interaction of endometrium with peritoneum is an important aspect of the disease process. Cell adhesion molecules (CAMs) are transmembrane receptors that facilitate intercellular binding and cellular interaction with the extracellular matrix (ECM). CAMs and components of the ECM are divided into large families based on sequence homology and similarity of tertiary structures. The function of eutopic and ectopic endometrial CAMs has been a focus of recent studies concerning the pathogenesis of endometriosis. Specific alterations in endometrial and peritoneal CAMs could facilitate binding of reflux menstruated endometrium at ectopic sites. In addition, the expression of CAMs by endometriotic lesions has been investigated to help understand mechanisms involved in the maintenance of endometrial tissue in ectopic locations. An understanding of the mechanisms involved in the interaction of endometrium with peritoneal tissues may provide new strategies to prevent endometriotic implants from forming and help treat existing lesions.