Cell adhesion to extracellular matrices is fundamental for maintaining normal tissue architecture and function. Many diseases are characterized, in part, by molecular changes in cell adhesion. These changes can occur as a result of modifications of the composition or integrity of the extracellular matrix or as a result of disease associated changes in the expression and/or function of adhesion receptors. Such alterations in cell adhesion can have profound effects on the phenotypic traits of cells, and as a result, these changes in cell adhesion can be of primary importance in facilitating disease-associated breakdown of normal tissue function. This is most apparent in a disease such as cancer, where neoplastic transformation can lead to alterations in tumor cell growth, changes in the composition or integrity of tissue proteins, tumor cell migration, invasion, and ultimately metastasis formation. Understanding the molecular basis of cell adhesion could lead to new insights into the molecular basis of many diseases, leading to better therapies. The purpose of this review is to highlight the role that collagens play in mediating cell adhesion, with an emphasis on the structural features of collagen important for cellular recognition and adhesion. Additionally, we briefly review the major receptors and intracellular signals that are important for cellular recognition of, and adhesion to, collagens.