Parabiosis, blood exchange and plasma transfer experiments have highlighted the rejuvenating properties of young blood. Our Communications Biology study demonstrated that young bone marrow transplantation attenuates cognitive decline in old mice, with preservation of hippocampal synapses and reduced microglial reactivity. We now discuss subsequent studies that shed additional light on how blood impacts cognitive function, and potential clinical applications, including ongoing clinical trials with young plasma and experimental strategies targeting the hematopoietic system to slow or reverse cognitive decline.