Small lipids such as eicosanoids exert diverse and complex functions. In addition to their role in regulating normal kidney function, these lipids also play important roles in the pathogenesis of kidney diseases. Increased glomerular cyclooxygenase (COX)1 or COX2 expression has been reported in patients with nephritis and in animal models of nephritis. COX inhibitors have shown beneficial effects on lupus nephritis and passive Heymann nephritis, but not anti-Thy1.1-induced nephritis. 5-Lipoxygenase-derived leukotrienes are involved in inflammatory glomerular injury. Lipoxygenase product 12-hydroxyeicosatetraenoic acid may mediate angiotensin II and transforming growth factor beta-induced mesangial cell abnormality in diabetic nephropathy. P450 arachidonic acid mono-oxygenase-derived 20-hydroxyeicosatetraenoic acid and epoxyeicosatrienoic acids are involved in several forms of kidney injury, including renal injury in metabolic syndrome. Ceramide also has been shown to be an important signaling molecule that is involved in the pathogenesis of acute kidney injury caused by ischemia/reperfusion and toxic insults. Those pathways should provide fruitful targets for intervention in the pharmacologic treatment of renal disease.