Have you ever wondered how drugs reach their targets and achieve their function within our bodies? If a drug molecule or a ligand is a message, an inbox is typically a receptor in the cell membrane. One such receptor involved in relaying molecular signals is a G protein-coupled receptor (GPCR). About one-third of existing drugs work by controlling the activation of this protein. Researchers now reveal a new way of activating GPCR by triggering shape changes in the intracellular region of the receptor. This new process can help researchers design drugs with fewer or no side effects.