This review offers an insight into recent studies on the structure and function of selectins, integrins and cadherins during cell-cell interactions and their involvement in signaling. The integrated roles of selectins, integrins, and cadherins are essential for many different biological processes and disease states such as tumor metastasis and autoimmune diseases. Selectins, integrins, and cadherins demonstrate their integrated roles in mediating leukocyte recruitment and migration to tissues across the endothelial and epithelial cell monolayers. With the exception of cadherin which is also involved in homophilic interactions, these key adhesion molecules are implicated in heterophilic interactions through the ligand binding recognition of their respective extracellular domains. Structure and function relationships of these molecules are important in modulating the mechanism of action and signalling properties of these adhesion molecules. Therefore available information on the structure and the cross-talk between these adhesion molecules is presented in this review.