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Integrins are a family of heterodimeric transmembrane receptors that mediate cell-cell and cell-extracellular matrix adhesion. Integrin-mediated signaling is essential for the regulation of fundamental cellular functions, including proliferation and survival, and for tumor development. According to in vitro studies, integrin ligation by extracellular matrix proteins can modulate the cytotoxicity of anti-tumor agents, in a cell-type sensitive manner. Underlying molecular mechanisms are not well understood, but may be based on the interrelations between integrin signaling pathways and pathways that control cell cycle and apoptosis. On the other hand, alterations of integrin expression and/or function have been observed during the acquisition of chemoresistance in cells chronically exposed to cytotoxic agents. These data are in favor of a role of integrins in chemoresistance processes, and open new perspectives in the field of cancer therapy and prognosis.