Neural membranes are composed of glycerophospholipids, sphingolipids, cholesterol and proteins. The distribution of these lipids within the neural membrane is not random but organized. Neural membranes contain lipid rafts or microdomains that are enriched in sphingolipids and cholesterol. These rafts act as platforms for the generation of glycerophospholipid-, sphingolipid-, and cholesterol-derived second messengers, lipid mediators that are necessary for normal cellular function. Glycerophospholipid-derived lipid mediators include eicosanoids, docosanoids, lipoxins, and platelet-activating factor. Sphingolipid-derived lipid mediators include ceramides, ceramide 1-phosphates, and sphingosine 1-phosphate. Cholesterol-derived lipid mediators include 24-hydroxycholesterol, 25-hydroxycholesterol, and 7-ketocholesterol. Abnormal signal transduction processes and enhanced production of lipid mediators cause oxidative stress and inflammation. These processes are closely associated with the pathogenesis of acute neural trauma (stroke, spinal cord injury, and head injury) and neurodegenerative diseases such as Alzheimer disease. Statins, the HMG-CoA reductase inhibitors, are effective lipid lowering agents that significantly reduce risk for cardiovascular and cerebrovascular diseases. Beneficial effects of statins in neurological diseases are due to their anti-excitotoxic, antioxidant, and anti-inflammatory properties. Fish oil omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, have similar anti-excitotoxic, antioxidant and anti-inflammatory effects in brain tissue. Thus the lipid mediators, resolvins, protectins, and neuroprotectins, derived from eicosapentaenoic acid and docosahexaenoic acid retard neuroinflammation, oxidative stress, and apoptotic cell death in brain tissue. Like statins, ingredients of fish oil inhibit generation of beta-amyloid and provide protection from oxidative stress and inflammatory processes. Collective evidence suggests that antioxidant, anti-inflammatory, and anti-apoptotic properties of statins and fish oil contribute to the clinical efficacy of treating neurological disorders with statins and fish oil. We speculate that there is an overlap between neurochemical events associated with neural cell injury in stroke and neurodegenerative diseases. This commentary compares the neurochemical effects of statins with those of fish oil.