In a recent study published in Nature, Daily et al. profiled parasite gene expression in Plasmodium falciparum infections and identified three in vivo ‘states’ based on parasite transcription patterns. Despite similar host clinical features, two states displayed highly divergent gene expression, whereas the third was found in individuals with increased inflammatory markers. These findings suggest that parasites exist in different physiological states in vivo, providing an important foundation for future studies investigating how these states might contribute to malaria pathogenesis and outcome.