Acute kidney injury (AKI) is common among hospitalized patients and is associated with high morbidity and mortality. Inflammation is recognized to play an important role in both ischemic and toxic models of AKI. Cisplatin is a widely used and highly effective cancer chemotherapeutic agent but carries the risk of nephrotoxicity. We have used a model of cisplatin-induced AKI to explore the functions of the innate immune response in kidney injury. Several components of innate immunity, such as Toll-like receptor sensing and inflammatory cytokine production, contribute to both ischemic and cisplatin-induced AKI. Importantly, it is the activity of these components in kidney parenchymal cells, rather than immune cells, which mediate AKI. Cellular components of innate immunity, such as neutrophils and dendritic cells, appear to play disparate roles in ischemic vs toxic AKI. Innate immune pathways could be targeted to prevent or treat AKI.