Intracellular signal transduction controlling neuronal development and survival is conveyed by second messengers that are often differentially regulated over space and time. The highly polarized morphology of neurons is conferred by a network of regulatory signaling pathways that determine axon guidance and dendrite formation. Among these, cyclic adenosine monophosphate (cAMP) is a second messenger that is critical for numerous neuronal functions and known to activate and integrate a variety of downstream pathways. In the central nervous system (CNS), cAMP-dependent signaling is involved in growth cone motility, neuro-nal metabolism, axon extension in vitro, neuroprotection, and survival in vivo. The complexity of cAMP-dependent neuronal physiology and function raises fundamental questions about the mechanisms deter-mining the specificity by which cAMP can regulate these processes. A growing body of evidence suggests that fidelity in cAMP signaling is often achieved by the temporal and spatial restriction of cAMP fluxes to discrete cellular compartments where cAMP diffusion is limited by phosphodiesterase-catalyzed degradation. Despite evidence showing the importance of cAMP for neuronal survival and axon pathfinding (Gold-berg et al., 2002), much remains to be learned regarding the architecture supporting cAMP compartmentation in neurons.