Cellular actions and fates—gene expression, differentiation, proliferation, apoptosis, and migration—are modulated by a sequence of signals that include the multiple adhesive contacts found between cells and their extracellular environment. A family of cell surface proteins, termed cell adhesion molecules, are important in mediating interactions. These proteins are segregated into distinct families with a wide range of physical properties. Some members exhibit strong binding properties, important for the maintenance of tissue integrity, whereas other members form weaker, more dynamic binding interactions, which are important during cellular migration processes. Research has demonstrated that these proteins are extremely versatile biological players, not only providing a form of cellular glue but also providing a means for coordinating a wide range of intracellular signaling events (including receptor tyrosine kinases and phosphatases), which have important functional consequences for processes as diverse as gene expression, cellular differentiation, migration, proliferation, and apoptosis. This review will briefly highlight the physical and biochemical properties that categorize cell surface molecules as adhesion molecules and demonstrate how these proteins form important modulators of cellular conversation by acting as assembly points for cytosolic adaptor proteins. The examples in this review are restricted to the signaling events coordinated by the integrin, immunoglobulin superfamily (Ig) cell adhesion molecules, cadherin/catenin families, and the selectins. These families exhibit a broad spectrum of biophysical and biochemical characteristics and yet all clearly demonstrate common dynamic interactions, forming multiprotein complexes linked to intracellular proteins and resultant signaling events.