Abstract: Epidemiological studies have reported an increased risk of Parkinson’s disease (PD) development in amphetamine-type stimulant users during their lifetime (Garwood et al., 2006; Rumpf et al., 2017). Protein inclusions mainly composed of misfolded and aggregated α-synuclein are the pathological hallmark of PD and other disorders known as synucleinopathies. Molecular studies present evidence that amphetamine upregulates α-synuclein synthesis in substantia nigra. The increment of α-synuclein levels promotes its aggregation and amyloid fibril formation, increasing  reactive oxygen species (ROS), and consequently dopamine oxidation (Wang and Witt, 2014), known to be toxic for dopaminergic neurons involved in motor function and limbic-motor integration. Over the years, these damaged cells lose their functionality and may die precociously, depleting the reserve of neural cells necessary for the normal neurological function which contributes to the onset of PD, when a critical number of cells are lost (Garwood et al., 2006). Therefore, the use of amphetamine-type stimulants may be a trigger event in the development of PD and parkinsonism, in conjugation to other risk factors that a given individual may hold. Despite the evidence, a previous study suggests that there is not enough data to corroborate the loss of dopamine neurons due to human amphetamine-type stimulant exposure, and consequently its implication in the PD development (Kish et al., 2017). Thus, elucidating the mechanisms underlying amphetamine-type stimulant influence on PD may contribute to better knowledge about the risk factors for the onset of this disease by these substances and adopt social policies to prevent future cases. The present perspective highlights the uncharted spots of the molecular mechanisms of α-synuclein aggregation pathways and how additional studies are necessary to understand the role of amphetamine-like stimulants as triggers of PD by changing α-synuclein thermodynamic and kinetic landscape.