Cell adhesions consist of multimolecular protein complexes of transmembrane adhesion receptors anchoring intracellular cytoskeletal structural proteins and signal transduction molecules. Recent advances reveal that components of cell adhesion complexes display multiple interactions and functions, which cooperate to mediate both cell adhesion and signaling. Cell-matrix and cell-cell adhesions can serve as both recipients and generators of signaling information, using hierarchical and synergistic molecular interactions regulated by aggregation, conformational changes, phosphorylation, and tension.