Neurodegeneration represents a looming crisis, as the number of people afflicted continues to increase and a limited understanding of diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, Parkinson’s disease, and dementia exists. The etiology of many of these diseases remains unknown, leading many scientists to consider that environmental factors may play a causal role. This chapter provides an overview of the epidemiological evidence of the potential role of formaldehyde in the pathogenesis of neurodegenerative diseases. We focus on the neurotoxic effects of formaldehyde in relevant human studies to understand potential associations. We also touch upon the findings from animal in/ex vivo studies, and in vitro studies to understand mechanistic disease progression. Further, we evaluate the weight of evidence and briefly discuss the potential mechanisms and contributors to neurodegeneration. Overall, our review of many individual studies supports the finding that formaldehyde exposure contributes to neurotoxicity. A number of studies reported an association of exposure to formaldehyde with ALS, although links with other neurodegenerative diseases are suggestive but inconclusive. Further studies are needed to confirm current findings and investigate underlying mechanisms. The findings summarized and discussed herein encourage hope that new, causative understandings of neurodegeneration will emerge.