Advances in Cancer Research, volume 153 provides a timely review of the biology, biochemistry, and current approaches to therapeutically target the RAS oncoprotein, the most frequently mutated oncogene family in human cancers. 2021 saw the approval of the first direct RAS inhibitor (sotorasib) for use in treating non-small cell lung cancers harboring KRAS(G12C) mutations. The successful approval and use of this drug highlights that the once “undruggable RAS is indeed pharmacologically tractable. This volume provides an overview of efforts to develop additional approaches to therapeutically target oncogenic RAS. In addition, the reader will find excellent reviews on the history and research efforts to understand the biochemistry and oncogenic activity of RAS in human cancers. Overview of the history and development of efforts to pharmacologically inhibit RAS. Discussion of the biochemistry and biology of different RAS mutant proteins and how this might be effectively leveraged in the development of anti-RAS therapies. Up-to-date reviews of the cutting-edge approaches to develop new anti-RAS pharmacologics.