Compelling evidence indicates that a key pathological event in Alzheimer’s disease is the misfolding and aggregation of normal soluble amyloid-β peptide into β-sheet-rich oligomeric structures which have a neurotoxic activity and ability to form insoluble amyloid deposits that accumulate in the brain. β-sheet breakers constitute a new class of drugs that are designed to specifically bind amyloid-β peptide blocking and/or reversing the misfolding process. In this article we review this approach and summarize the data supporting the view that β-sheet breakers could be serious candidates to combat this devastating disease.