Integrins are a large family of cell surface receptors that bind extracellular matrix proteins. The interaction of integrins with extracellular matrix activates a number of intracellular signaling pathways involved in cell proliferation, differentiation, motility, and other essential cell functions. Integrins are critically important to both health and disease. In this review, we first describe the structure, functions, and signaling characteristics of integrins. We then discuss the roles of integrins in cancer progression. Finally, we recapitulate the laboratory and clinical efforts of targeting integrins as effective means of cancer therapy and diagnosis. This comprehensive review could help scientists and clinicians gain a complete understanding of integrins. It could also contribute toward the development of new drugs, new methods of diagnostics, and new treatment of cancers to benefit the patients in clinical practice.