The “misfolding” and assembly of proteins into various types of ordered and amorphous aggregates has been implicated in a wide range of both detrimental and beneficial biological functions. Although much less is known about protein misfolding than protein folding, it appears that the molecular interactions involved in these two processes are very different. To further illuminate the molecular determinants of misfolding, we have sought to understand the underlying protein-protein interactions. We find that peptide microarrays can be used to identify small elements of amino-acid sequence within several amyloid-forming proteins that govern their aggregation behavior. Moreover, we find that different environmental conditions (e.g., temperature) and mutations favor certain pathways by activating or inhibiting specific protein-protein interactions, and that the resulting assembled structures have distinct physical and biological properties. In the future it may be possible to use peptide microarrays to identify inhibitors of protein aggregation by targeting specific protein-protein interactions.