The ability to form stable cross-beta fibrils is an intrinsic physicochemical characteristic of the human beta-amyloid peptide (A beta), hich forms the brain amyloid of Alzheimer’s disease (AD). The high amyloidogenicity and low solubility of this hydrophobic approximately 40-mer have been barriers to its study in the past, but the availability of synthetic peptide and new physical methods has enabled many novel approaches in recent years. Model systems for A beta aggregation (relevant to initial nidus formation) and A beta deposition (relevant to plaque growth and maturation) in vitro have allowed structure/activity relationships and kinetics to be explored quantitatively, and established that these processes are biochemically distinct. Different forms of the peptide, with different physiochemical characteristics, are found in vascular and parenchymal amyloid. Various spectroscopic methods have been used to explore the three-dimensional conformation of A beta both in solution and in solid phase, and demonstrated that the peptide adopts a different configuration in each state. A significant conformational transition is essential to the transformation of A beta from solution to fibril. These observations suggest new therapeutic targets for the treatment of AD.