The aggregation of a-synuclein (a-syn) into amyloid fibrils is associated with neurodegenerative diseases, collectively referred to as the a-synucleinopathies. In vivo, molecular chaperones, such as the small heat-shock proteins (sHsps), normally act to prevent protein aggregation; however, it remains to be determined how aggregation-prone a-syn evades sHsp chaperone action leading to its disease-associated deposition. This work examines the molecular mechanism by which two canonical sHsps, aB-crystallin (aB-c) and Hsp27, interact with aggregation-prone a-syn to prevent its aggregation in vitro. Both sHsps are very effective inhibitors of ¿-syn aggregation, but no stable complex between the sHsps and a-syn was detected, indicating that the sHsps inhibit a-syn aggregation via transient interactions. Moreover, the ability of these sHsps to prevent a-syn aggregation was dependent on the kinetics of aggregation; the faster the rate of aggregation (shorter the lag phase), the less effective the sHsps were at inhibiting fibril formation of a-syn. Thus, these findings indicate that the rate at which a-syn aggregates in cells may be a significant factor in how it evades sHsp chaperone action in the a-synucleinopathies.