The predominant accumulation of aggregated proteins is observed in neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. Protein misfolding and aggregation is strongly regulated by molecular chaperones known as heat shock proteins (HSPs) including Hsp90, Hsp70, Hsp27, Hsp60, and Hsp40 among others. Recent research activity indicates that expression and activation of HSPs may prevent or reduce protein aggregation in Alzheimer’s disease, Parkinson’s disease, Polyglutamine disease, Prion disease, and other neurodegenerative disorders. In the present review, laboratory findings that implicate the role of HSPs in the development of neurodegeneration will be discussed. Furthermore, strong experimental evidence presented here show that expression and/or increased activation of HSPs by phytochemicals may prevent various neurodegeneration through preventing protein aggregation process and reduce the toxicity of the oligomers. Molecular consequences of altered gene products, protein, glucose and lipid oxidation due to disrupted redox homeostasis lead to accumulation of unfolded and misfolded protein in the aging brain. Neurodegenerative diseases including Alzheimer’s, Parkinson’s, Huntington, and Friedreich ataxia share, a common denominator, production of abnormal proteins, mitochondrial dysfunction and oxidative stress. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are two most prevalent neurodegenerative diseases that affect the elderly population. Aggregation of β-amyloid and hyperphosphorylation and subsequent tangle formation of tau protein is believed to promote Alzheimer’s disease [1,2], and tau suppression in a neurodegenerative mouse model improves memory function [3]. The exact cause of PD remains obscure, however, genes encoding α-synuclein, LRKK2, Parkin, DJ1, PINK1, ATP13A2, VPS35, FBXO7, GBA and EIF4G1 are implicated in the pathogenesis of and susceptibility to PD [4]. There is strong evidence that α-synuclein aggregation is an early step in the pathogenesis of PD [5]. α -Synuclein appears to be toxic upon overexpression and during misfolding or subsequent oligomerization [6].