Cyclic adenosine monophosphate (cAMP) is a second messenger of paramount biological importance, involved in the regulation of a significant number of cellular functions through the cAMP-dependent intracellular signal transduction pathways. The aim of this "Frontiers in Pharmacology" Research Topic was to attract contributions that highlight emerging ideas in the cAMP field that: (i) describe its role in cellular function and homeostasis, (ii) present the current approaches to its pharmacological manipulation, and (iii) clarify its central role in the development of more targeted therapeutic approaches toward a spectrum of diseases. The present collection of articles highlights, in a representative (but certainly not exhaustive) way, the research activity and emerging concepts in the field, while it also reveals the therapeutic potential that targeted pharmacological manipulation of intracellular cAMP levels could exert on a number of pathological conditions.