Protein serine/threonine phosphatases (PSTPs) are considered undruggable due to their conserved catalytic site and broad substrate specificity. Protein phosphatase-1 (PP1) is a ubiquitous PSTP that is predicted to catalyze a majority of Ser and Thr dephosphorylations in eukaryotic cells. PP1 has broad substrate specificity but is restrained in vivo by numerous PP1-interacting proteins functioning for example as substrate-targeting proteins and forming specific holoenzymes with PP1. PP1 holoenzymes play a role in many different diseases such as cancer (counteracting oncogenic kinases), diabetes (insulin release) and HIV (viral translation). We recently developed the first compound, a peptide, that selectively activates PP1 in intact cells by disrupting protein-protein interactions of PP1 and its regulatory proteins. The activator does not act on the most closely related protein phosphatases 2A and 2B. I will introduce the PP1-disrupting peptides including applications such as counteracting oncogenic kinase signaling.