Cells adhere to the extracellular matrix throughout most of their lifetime. This close, intimate contact with the matrix exerts an extraordinary control on the behavior of cells, determining whether they move or stay put, proliferate or remain quiescent, and even live or die. Attachment to the matrix not only enables cells to respond to soluble growth factors and cytokines but also determines the nature of the response. The integrins are a large family of receptors that attach cells to the matrix, organize their cytoskeleton, and cooperate with receptor protein tyrosine kinases to regulate cell fate. Research on integrin signaling is beginning to explain the complex and specific effects that the extracellular matrix exerts on cells.