To orchestrate development and maintain tissue homeostasis, multicellular organisms have evolved a large number of cell adhesion molecules (CAMs). There are four major classes of CAMs: the immunoglobulin superfamily (IgSF), the cadherins, the integrins and the selectins. The diverse structures and functions of CAMs provide vital yet profound cellular basis for guidance or anchorage-dependent growth, cell indentity recognition and signal transduction. Malfunctions of CAMs have been linked to a broad range of diseases such as cancer, vasculo- and immuno-pathies, epithelial and neurological disorders. Recent studies have revealed the mechanistic details of many CAMs. In this chapter, we summarize the cellular and molecular mechanisms that have contributed to our understandings of CAMs in various physiological and pathological processes.