Synopsis: Phosphoryl transfer reactions are one of the most important chemical transformations in biology and central to key cellular processes such as signal/energy transduction and gene duplication/transcription. Enzymes and RNAs that catalyze phosphoryl transfer rich of compelling mechanistic questions at many scales and answering these questions is beneficial to the understanding of not only specific enzymes but also general strategies that Nature employs to evolve complex biological functions. This workshop brings together theoreticians and experimentalists to discuss key open questions in the field. An overarching objective of the workshop is to stimulate discussions aimed at developing innovative strategies that integrate theory and experiment to tackle fundamental mechanistic challenges. Such strategies are required to systematically improve the accuracy of computational (both classical and QM/MM) models, aid in the interpretation of kinetic isotope effects and linear free energy relations for the characterization of transition states, and assess the contributions from structural and electrostatic features to catalysis. In this way, we hope to facilitate new science at the interface of theory and experiment, aimed at providing deeper insight into the mechanisms of biological phosphoryl transfer reactions.