The Kirsten rat sarcoma viral oncogene homolog (KRAS) is mutated in about a quarter of all human cancers and is at the centre of several pathways involved in tumorigenesis. As such, novel therapeutic strategies that can target this oncoprotein are potentially extremely valuable. However, since its discovery as on oncogene, almost four decades have gone by without any major breakthrough in the therapeutic targeting of mutant KRAS. In recent years, however, we are finally witnessing a paradigm shift with the discovery of druggable pockets on KRAS and the clinical activity of covalent KRASG12C inhibitors such as sotorasib and adagrasib.