Some of the cruelest and most devastating disorders known to humans are those linked to neurodegeneration, which result in the loss of neurons that are critical for body and brain function. Examples of these include Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Prion disease, amyotrophic lateral sclerosis and other neurological and psychiatric disorders. Recent estimates suggest that one in four Americans will suffer from a neurodegenerative disorder, and this number is likely to rise because of an increase in life expectancy. Although once thought to be intractable, research into neurodegenerative diseases is yielding new clues, not only in terms of the genes and pathways that are linked to neurodegeneration, but also in ways to prevent and treat these disorders. Our current understanding of neurodegeneration indicates it is brought about by three main influences, genetic (genes), environmental, and aging itself. Modern advances in molecular, structural, computational, biochemical, electrophysiological, systems biology and stem cell techniques are providing new insight and avenues to model and treat neurodegeneration. There is great hope and excitement that the next few years will witness the development of rational therapies to treat and/or prevent neurodegenerative diseases.