•cAMP signalling is an essential messenger system in the regulation of pituitary physiology.•De-regulation of cAMP pathways leads to pituitary tissue proliferation.•cAMP signalling interacts with various other cellular cascades.•Somatic mutations and molecular aberrations altering cAMP signalling induce tumorigenesis.•Novel mechanisms of cAMP deregulation are discussed. cAMP signalling plays a key role in the normal physiology of the pituitary gland, regulating cellular growth and proliferation, hormone production and release. Deregulation of the cAMP signalling pathway has been reported to be a common occurrence in pituitary tumorigenesis. Several mechanisms have been implicated including somatic mutations, gene–gene interactions and gene–environmental interactions. Somatic mutations in G-proteins and protein kinases directly alter cAMP signalling, while malfunctioning of other signalling pathways such as the Raf/MAPK/ERK, PI3K/Akt/mTOR and Wnt pathways which normally interact with the cAMP pathway may mediate indirect effects on cAMP and varying downstream effectors. The aryl hydrocarbon receptor signalling pathway has been implicated in pituitary tumorigenesis and we review its role in general and specifically in relation to cAMP de-regulation.