Peripheral membrane proteins are required for signal propagation upon ligand-induced receptor activation at the plasma membrane. The translocation of this amphitropic peripheral proteins from or to the plasma membrane enables signal cascade propagation into the cells. This translocation greatly depends on the membrane’s lipid composition and, consequently, regulation of the lipid bilayer emerges as a novel therapeutic strategy. Indeed, relevant changes in membrane lipids can induce massive translocation of peripheral signaling proteins from or to the plasma membrane, which controls how cells behave. We called these changes “lipid switches”, as they alter the cell’s status (e.g., proliferation, differentiation, death, etc.) in response to the modulation of membrane lipids. This discovery enables therapeutic interventions focused on modifying the bilayer’s lipids, an approach known as membrane-lipid therapy (MLT) or melitherapy.