Abstract In the present review we summarize recent advances in the understanding of the interaction between genetics and environmental factors involved in complex multi-factorial neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic Lateral Sclerosis (ALS). The discovery of several genes responsible for the familial forms has led to a better comprehension of the molecular pathways involved in the selective neuronal degeneration which is specific for each of these disorders. However, the vast majority of the cases occurs as sporadic forms, likely resulting from complex gene–gene and gene–environment interplay. Several environmental factors, including, pesticides, metals, head injuries, lifestyles and dietary habits have been associated with increased disease risk or even with protection. Hundreds of genetic variants have been investigated as possible risk factors for the sporadic forms, but results are often conflicting, not repeated or inconclusive. New approaches to environmental health research are revealing us that at the basis there could be chemically induced changes in gene regulation and emphasise the importance of understanding the susceptibility of the human epigenome to dietary and other environmental effects.