The cAMP-dependent kinase (PKA) is a broad specificity kinase that controls several fundamental processes in the heart including the strength and the frequency of contraction, the duration of the cardiac action potential as well as the activation of signaling pathways associated with the onset of cardiac hypertrophy and heart failure. It is now appreciated that to perform these functions, PKA must be precisely targeted in proximity to its cellular substrates. Evidence collected over the last years demonstrates that compartmentalization of the kinase is achieved through the association with A-kinase anchoring proteins (AKAPs). This family of functionally related proteins organize multivalent signaling complexes that target PKA and other signaling enzymes at precise subcellular sites within cardiomyocytes where they can be accessed by activators and, in turn, phosphorylate and modulate particular substrates.