Several advances in our understanding of pediatric cerebral malaria (CM) have been made over the past 25 years. Accurate clinical diagnosis is enhanced by the identification of a characteristic retinopathy, visible by direct or indirect ophthalmoscopy, the retinal changes (retinal whitening, vessel color changes, white-centered hemorrhages) being consistently associated with intracerebral sequestration of parasites in autopsy studies. Autopsies have yielded information at tissue levels in fatal CM, but new insights into critical pathogenetic processes have emerged from neuroimaging studies, which, unlike autopsy-based studies, permit serial observations over time and allow comparisons between fatal cases and survivors. Brain swelling has emerged as the major risk factor for death, and, among survivors, brain volume diminishes spontaneously over 24-48 hours. Studies of life-threatening and fatal malaria are suggesting new approaches to identifying and caring for those at highest risk; potential adjuvants should be evaluated and implemented where they are most needed.