BH3-only proteins: Orchestrators of apoptosis

► The diversity in the structures of BH3-only proteins reflects a range of functions. ► The mechanism(s) and importance of BH3-only proteins binding to membranes. ► BH3-only proteins activate and inhibit multi-region Bcl-2 family proteins. ► BH3-only proteins at the endoplasmic reticulum function in apoptosis and autophagy. ► BH3-mimetics are potential drugs for cancer therapy.