The integrins are a family of adhesion receptors involved in many physiological functions. These molecules are characterized by an ability to dynamically regulate their ligand binding affinity. Several integrins become "activated" or achieve the high affinity state in response to extracellular agonists or signals. High affinity ligand binding does not result from an increase in receptor number or from changes in the receptor microenvironment. Rather, evidence suggests these altered affinity states result from the varied conformations of these molecules. Understanding how these conformational changes are achieved remains an area of great interest in the field. In this review, we will discuss several means and potential mechanisms of integrin activation. First, we will focus on "activators" such as antibodies, peptides, and cations. For the most part, these agents can be viewed as nonphysiological activators that directly effect integrin conformational changes. Later we will discuss how conformational changes are achieved in a physiological sense. Many physiological activators stimulate signal transduction pathways inside the cell and are believed to transmit these signals outward to effect conformational changes. An understanding of integrin activation mechanisms is important as it might suggest ways to regulate cell adhesion in pathology and disease.