The Maillard reaction is a complex cascade of reactions initiated by glycation or the spontaneous reaction between the free amino groups of proteins and reducing sugars. The cascade reaction leads to the production of the so-called ‘advanced glycation end-products’ (AGEs), which include brown pigments, fluorescent compounds, free radicals and cross-linked protein products.While a role for protein glycation and AGEs in the complications associated with diabetes mellitus has been established, it is now becoming clear that the Maillard reaction may have a more widespread importance in human disease, especially those disorders typified by amyloidosis. Many of the properties of products of the Maillard reaction are also found in the brain lesions that characterise Alzheimer's disease, namely neuritic plaques and neurofibrillary tangles. AGE-modified tau and amyloid &bgr;-protein (A&bgr;) are both found in the brains of patients with Alzheimer's disease. Glycation of tau inhibits its normal microtubule-binding functions, while glycated A&bgr; serves to accelerate the nucleation of aggregated A&bgr;. Glycated tau can generate oxygen-free radicals in cell culture, and biomarkers of neuronal protein oxidation co-localise with the neuropathological hallmarks of Alzheimer's disease. These findings are consistent with the involvement of glycation and glyco-oxidation in the generation of these lesions from normal cellular proteins.Inhibitors of the Maillard reaction, such as pimagedine (aminoguanidine), are currently being assessed in clinical trials for the treatment of diabetic complications. In contrast, their potential for the treatment of Alzheimer's disease is only just being recognised, although the ability of these agents to cross the bloodbrain barrier may limit their therapeutic use. Tenilsetam, a compound shown to improve cognitive function in patients with Alzheimer's disease, has been found to inhibit glycation-induced protein cross-linking, as have the anti-inflammatory compounds indomethacin and aspirin (acetylsalicylic acid), drugs that have also shown therapeutic potential in Alzheimer's disease.These recent studies extend the therapeutic potential of inhibitors of the Maillard reaction to Alzheimer's disease. They also indicate possible neuroprotective approaches to the disease based on inhibition of the action of AGEs by the use of AGE-binding compounds and the modulation of AGE-cross-linked protein degradation. Finally, the pathological role of glycation in Alzheimer's disease implicates a disorder of metabolism as a primary defect in the disease, and offers the prospect of prophylaxis and improved diagnosis.