Adhesion molecules play a major role in many biological and pathological processes and are essential to the development and construction of tissue architecture. During inflammatory processes, adhesion molecules are also pivotally involved in both cell migration and cell activation through the involvement in the two reverse directional signaling; 1) the expression or function of adhesion molecules is regulated through "inside-out" signaling which is induced by the stimulation such as cytokines, 2) adhesion molecules not only function as a glue but also transduce extracellular information into cytoplasmic organelle through "outside-in" signaling, which induces cellular activation. The concept concerning adhesion molecules would bring enormous benefits to clarify pathological processes of various inflammatory diseases and cancer metastasis as well as the new pharmacological approaches to these diseases.