Reversible phosphorylation is a primary mode of signal transduction vital to all aspects of cellular function. Tightly controlled by the opposing activities of phosphatases and kinases, this post-translational modification mediates protein-protein interactions and regulates catalytic activity of enzymes. Disruption of this delicate balance can have profound pathological consequences. Stigmatized as nonselective house-keeping enzymes with limited druggability, protein phosphatases have emerged as equally important to kinases in health and disease. The aim of this EMBO Workshop is to bring together leading scientists and trainees in reversible phosphorylation, signal integration and drug discovery to present and discuss their latest findings, challenges and gaps in our knowledge. Topics will include protein phosphatases in immunobiology and immunotherapy, cancer biology and structure-function. A special session will be dedicated to innovative ways of targeting this family of enzymes and potential therapeutic benefit, and tributes will be given to pioneers of the field.