Ferric iron (Fe³⁺) enters mammalian cells complexed to transferrin, and after reduction to the ferrous form (Fe²⁺), it is translocated to the cytosol by endosome transporters. Fe²⁺ is rapidly utilized for metabolic pathways such as heme and iron-sulfur cluster protein biosynthesis or oxidized to Fe³⁺ and stored as a complex with ferritin. This scenario makes access to available iron very challenging for intracellular pathogens. Paiva et al. show that oxidative stress in macrophages promotes the intracellular growth of T. cruzi, by a mechanism that may involve releasing Fe²⁺ from ferritin, or from heme and/or iron-sulfur cluster proteins. Tf-R indicate transferrin receptor.