Adenylate cyclase integrates positive and negative signals that act through G protein-coupled cell-surface receptors with other extracellular stimuli to finely regulate levels of cAMP within the cell. Recently, the structures of the cyclase catalytic core complexed with the plant diterpene forskolin, and a cyclase-forskolin complex bound to an activated form of the stimulatory G protein subunit Gs alpha have been solved by X-ray crystallography. These structures provide a wealth of detail about how different signals could converge at the core cyclase domains to regulate catalysis. In this article, William Simonds reviews recent advances in the molecular and structural biology of this key regulatory enzyme, which provide new insight into its ability to integrate multiple signals in diverse cellular contexts.