There are many different types of cells in the body that dynamically interact with each other in a myriad of ways. These interactions, achieved via adhesion molecules, must be precisely and carefully controlled in time and space to correctly determine the structures and functions of tissues in a complex organism. It is not surprising, therefore, that cell-cell and cell-ECM adhesion molecules exhibit diverse structures, or that their expression levels vary in different cells and tissues. As a consequence, they mediate the very specific and distinctive cell-cell and cell-ECM interactions that hold tissues together as well as permit essential communication between cells and their environment. We begin this overview with a brief orientation to the various types of adhesion molecules present on cells and within the extracellular matrix, their major functions in organisms, and their evolutionary origin. In subsequent sections, we will examine in detail the unique structures and properties of various participants in cell-cell and cell-matrix interactions.