The search for a cure of Alzheimer's dementia is restless. In recent years, unexpected epidemiological data showing a protective effect of anti-inflammatory and cholesterol-lowering drugs gave way to clinical trials with these compounds. Now, a newly described mechanism indicating that brain amyloid clearance is modulated by serum insulin-like growth factor I may also lead to new trials with this growth factor. Insulin-like growth factor I is an abundant circulating hormone with potent central actions whose levels in serum appear to be altered in Alzheimer's patients. Amyloid clearance, a potential therapeutic target in Alzheimer's disease was mostly neglected until recent antiamyloid therapies proved to involve a peripheral amyloid sink. Although more work in animal models are required, the evidence available strongly indicates that insulin-like growth factor I therapy in Alzheimer's dementia may be addressing pathogenic processes.