There is overwhelming evidence that the reversible phosphorylation of proteins regulates most aspects of cell life. However, the broad specificities displayed by many protein phosphatases and kinases in vitro dictates that their activities be strictly regulated in vivo. Recent evidence indicates that a novel class of proteins, known as targetting subunits, specifies the location, catalytic and regulatory properties of protein phosphatases and kinases, and thereby plays a key role in ensuring the fidelity of protein phosphorylation.