Amyloid beta-protein (A beta) oligomers are broadly viewed as the proximate mediators of toxicity in Alzheimer's disease (AD). Recent studies, however, provide substantial evidence that A beta is involved in protection and repair of the central nervous system whereby A beta oligomer and subsequent fibril formation are integral to its normal antimicrobial and antiviral function. These developments raise a question of what exactly makes A beta oligomers toxic in the context of AD. This Perspective describes a paradigm shift in the search for toxic A beta oligomer species that involves oxidative-stress-induced stabilization of A beta oligomers via cross-linking and reviews most recent research elucidating structural aspects of cross-linked A beta oligomers and potential inhibition of their toxicity.