Protein phosphorylation and dephosphorylation are two essential and vital cellular mechanisms that regulate many receptors and enzymes through kinases and phosphatases. Ca2+- dependent kinases and phosphatases are responsible for controlling neuronal processing; balance is achieved through opposition. During molecular mechanisms of learning and memory, kinases generally modulate positively while phosphatases modulate negatively. This review outlines some of the critical physiological and structural aspects of kinases and phosphatases involved in maintaining postsynaptic structural plasticity. It also explores the link between neuronal disorders and the deregulation of phosphatases and kinases.