Ferroptosis is a form of programmed cell death with particular hallmarks, such as oxidative stress, increased calcium fluxes, and altered cellular morphology. In ferroptosis, the disruption of plasma membrane is the step that culminates into cell death. By inducing ferroptosis with Erastin-1 and RSL3 in various human cellular models, Pedrera et al. tracked the behaviour of several hallmarks of ferroptosis and demonstrated that lipid peroxidation precedes cytosolic calcium rise and plasma membrane breakdown, which is dependent on nanopore formation. Ferroptotic cell death is inhibited by osmotically active protectants of proper size that can prevent water flux through nanopores.