The FGFR family of receptors are well-validated targets in cancer, and several pan-FGFR inhibitors that have strong activity against FGFR1-4 have reached approval. While specific FGFRs like FGFR2 can drive cancers like cholangiocarcinoma, broad inhibition of FGFRs leads to significant off-target toxicities, such as hyperphosphatemia from FGFR1 inhibition or diarrhea from FGFR4 inhibition. Relay Therapeutics captured industry attention when they announced the discovery of an FGFR2 isoform-selective inhibitor, lirafugratinib, using a molecular dynamics simulations approach. This article provides an overview of the pan-FGFR landscape, explores the specifics of the FGFR2 selectivity, preclinical pharmacology, and early clinical data for this remarkable molecule.