This review discusses aspects of known and putative compartmentalized 3',5'-cyclic adenosine monophosphate (cAMP) signaling in astrocytes, a cell type that has turned out to be a key player in brain physiology and pathology. cAMP has attracted less attention than Ca2+ in recent years, but could turn out to rival Ca2+ in its potential to drive cellular functions and responses to intra- and extracellular cues. Further, Ca2+ and cAMP are known to engage in extensive crosstalk and cAMP signals often take place within subcellular compartments revolving around multi-protein signaling complexes; however, we know surprisingly little about this in astrocytes. Here, we review aspects of astrocytic cAMP signaling, provide arguments for an increased interest in this subject, suggest possible future research directions within the field, and discuss putative drug targets.