The amyloid and tangle cascade hypothesis is the dominant explanation for the pathogenesis of Alzheimer's disease (AD). A complete knowledge of the metabolic pathways leading to beta-amyloid (A beta) production and clearance in vivo and of the pathological events that lead to fibril formation and deposition into plaques is crucial for the development of an 'anti-amyloid' therapeutic strategy. Important advances in this respect have been achieved recently, revealing new candidate drug targets. Among the most promising potential treatments are beta- and gamma-secretase inhibitors, A beta vaccination, Cu-Zn chelators, cholesterol-lowering drugs and non-steroidal anti-inflammatory drugs. Now, the major question is whether these drugs will work in the clinic.