Integrins are a family of heterodimeric proteins expressed by cardiac fibroblasts and cardiomyocytes that provide critical adhesive and signaling functions through their interactions with the extracellular matrix (ECM) and the actin cytoskeleton. These adhesive processes are important for paracrine signaling, ECM homeostasis and for the intercellular interactions that impact cardiac cell biology and pathophysiological adaptation in disease. Despite considerable progress, our understanding of the interplay between cardiac cells, the ECM and integrins remains largely elusive. In this review, we examine the role of integrins in adhesive and signaling functions, and how these functions enable communication between cardiac fibroblasts, cardiomyocytes and the ECM. These processes strongly influence cardiac development and, later, the progression into cardiac disease. An improved understanding of this multi-dimensional system in cardiac tissues is needed to decipher the biological, spatiotemporal and mechanical cues that regulate cardiac health and the manifestation of cardiac disease. Greater insight into integrin function in cardiac tissues may also suggest new treatments for the prevention of heart failure.