Aggregated a-synuclein is the major component of inclusions in Parkinson's disease and other synucleinopathy brains indicating that a-syn aggregation is associated with the pathogenesis of neurodegenerative disorders. Although the mechanisms underlying a-syn aggregation and toxicity are not fully elucidated, it is clear that a-syn undergoes post-translational modifications and interacts with numerous proteins and other macromolecules, metals, hormones, neurotransmitters, drugs and poisons that can all modulate its aggregation propensity. The current and most recent findings regarding the factors modulating a-syn aggregation process are discussed in detail.