Necroptosis is a form of programmed necrotic cell death that is rapidly emerging as an important pathophysiological pathway in numerous disease states. Necroptosis is dependent on receptor-interacting protein kinase 3 (RIPK3), a protein shown to play an important role in experimental models of critical illness. RIPK3 promotes kidney tubular injury via mitochondrial dysfunction. The FAO-dependent RIPK3 mediates pathogenesis of acute lung injury.