The “second messenger” archetype cAMP is one of the most important cellular signalling molecules with central functions including the regulation of insulin and glucagon secretion from the pancreatic β‐ and α‐cells, respectively. cAMP is generally considered as an amplifier of insulin secretion triggered by Ca²⁺ elevation in the β‐cells. Both messengers are also positive modulators of glucagon release from α‐cells, but in this case cAMP may be the important regulator and Ca²⁺ have a more permissive role. The actions of cAMP are mediated by protein kinase A (PKA) and the guanine nucleotide exchange factor Epac. The present review focuses on how cAMP is regulated by nutrients, hormones and neural factors in β‐ and α‐cells via adenylyl cyclase‐catalysed generation and phosphodiesterase‐mediated degradation. We will also discuss how PKA and Epac affect ion fluxes and the secretory machinery to transduce the stimulatory effects on insulin and glucagon secretion. Finally, we will briefly describe disturbances of the cAMP system associated with diabetes and how cAMP signalling can be targeted to normalize hypo‐ and hypersecretion of insulin and glucagon, respectively, in diabetic patients.