Protein kinase A (PKA) is the archetypical phosphokinase, sharing a catalytic core with the entire protein kinase superfamily. In eukaryotes, the ubiquitous location of PKA makes it one of the most important cellular signaling molecules, involved in a myriad of events. The catalytic subunit of PKA (PKA‐C) is one of the most studied enzymes and was the first kinase to be crystallized; however, the effects of ligand binding, post‐translational modifications and mutations on the activity of the kinase have been difficult to understand with only structural data. Here, we review our latest NMR studies on PKA‐C, the results of which underscore the role of fast and slow conformational dynamics in the activation and inhibition of the kinase.