cAMP/PKA signalling modulates contractile, metabolic and transcriptional cellular responses. This signalling system is at the core of the neuro-hormonal regulation of cardiovascular functions and is the target of a number of current therapeutics. The pleiotropic effects of cAMP/PKA signals rely on an intricate intracellular network of simultaneously operating pathways that are uniquely regulated to deliver the signal to the appropriate subcellular location. Local control (compartmentalisation) of cAMP/PKA signalling allows for only a section of the network to be active at any given time and determines the specificity and accuracy of the functional response. Disruption of cAMP/PKA signalling compartmentalisation associates with development of disease. By combining real-time FRET imaging, genetic, biochemical and mathematical approaches we are mapping cAMP/PKA subcellular signalling domains in cardiac myocytes, we are establishing their function and regulation and determining how local signalling is altered in pathological conditions. Our ultimate goal is to develop precision medicine strategies to target local cAMP pools, rather than global intracellular cAMP levels, to achieve greater therapeutic efficacy and specificity. Our recent studies in cardiac myocytes reveal a previously unsuspected sub-microscopic heterogeneity of intracellular cAMP signals and provide evidence that the physiologically relevant cAMP is confined to nano-domains immediately surrounding effector-target complexes. These findings subvert the classical notion of cAMP signalling and provide a new framework for the development of targeted therapeutic approaches.