Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and Huntington's disease, are a group of age-dependent, progressive disorders that exhibit prominent neuronal death. Alzheimer's disease and Parkinson's disease are mainly sporadic, whereas Huntington's disease is entirely genetic. Studies on human postmortem brains highlighted the possible involvement of apoptosis and autophagy in neuron death in the diseases. Studies using genetically engineered mouse models confirmed contributions of key apoptosis genes in disease progression in these experimental systems. In addition, mouse models confirmed that neurotoxins may accelerate and exacerbate disease progression. A better understanding of neuron death mechanisms in these diseases will help design better treatment strategies.