Individual cells in multicellular organisms constantly explore their microenvironment, or niche, to obtain spatial information that is used to regulate cell behavior to maintain tissue integrity. The extracellular matrix (ECM) is an important source of such spatial information. Binding of the integrin family receptors to the ECM triggers formation of integrin adhesion complexes (IACs) that link the ECM network to cellular cytoskeleton via remarkably large multiprotein complexes collectively referred to as the integrin adhesome. Recent advances in proteomics have enabled researchers to study the IAC composition in detail. Various biochemical IAC isolation methods and culture conditions have been employed to study the composition and dynamics of integrin-mediated adhesions mainly in fibroblasts and lymphoblasts. These studies have led to identification of daunting lists of potential IAC components. This review focuses on the current status of proteomics-driven research seeking to understand integrin functions by comprehensive analysis of IAC components. These systems level approaches have revealed the complexity of biochemical and biomechanical signals that are processed at IACs and provide a novel insight into how these signals are conveyed to regulate cellular behavior.