RAS proteins are binary switches, cycling between ON and OFF states during signal transduction. These switches are normally tightly controlled, but in RAS-related diseases, such as cancer, RASopathies, and many psychiatric disorders, mutations in the RAS genes or their regulators render RAS proteins persistently active. The structural basis of the switch and many of the pathways that RAS controls are well known, but the precise mechanisms by which RAS proteins function are less clear. All RAS biology occurs in membranes: a precise understanding of RAS’ interaction with membranes is essential to understand RAS action and to intervene in RAS-driven diseases. RAS proteins have been linked to several cancers. The identification of RAS regulatory proteins has provided deeper insights into the biochemical and biophysical properties of RAS proteins as well as shed light into ways to target them pharmacologically.