Recently, our efforts have been dedicated to the study of the structure of amyloid aggregates as well as to the molecular basis of protein folding, misfolding and aggregation and the cell biology of aggregate cytotoxicity to living systems. These studies have mainly been carried out on model proteins and peptides such as acylphosphatases, β2-microglobulin, Ure2p, Sup35, amylin and Aβ peptides. Amyloid is mainly composed of ordered β-sheet-rich polymeric assemblies of specific peptides and proteins found in tissues and organs of people affected by a subset of degenerative diseases known as amyloidoses. Our recent research has provided significant contributions to establish new ideas on this field including the following: (i.) most, possibly all peptide and protein may polymerize into assemblies undistinguishable from amyloids; (ii.) the rate of aggregation from unfolded states of mutant proteins/peptides depends on the alteration, of specific physicochemical features such as mean hydrophobicity, net charge and propensity to beta structure; (iii.) these assemblies are toxic to cultured cells and to living organisms in their pre-fibrillar organization similarly to aggregates of peptides and proteins associated with disease; (iv.) they impair cell viability through early modifications of the same biochemical parameters (notably intracellular redox status and free calcium concentration) as previously reported for aggregates of peptides and proteins associated with amyloid diseases; (v.) the apoptotic or necrotic outcome seems to depend on the timing of the involvement of the mitochondria; (vi.) the different vulnerability to the same aggregates shown by varying cell types are associated with the cell-specific biochemical equipment and the different content of membrane lipids (notably cholesterol and GM1) and proteins; (vii.) amyloid oligomer cytotoxicity as a property which emerges from the interplay between the biophysical features of the interacting oligomers and cell membranes.