The phenomenon in which any peptide or protein fails to achieve its native conformation forms are referred as protein misfolding. Since protein regulate innumerable cellular processes and act as a molecular machine, thus, improper folding can abrogates its proper biological functioning. This impairment in folding results in the aggregation and insolubilization that finally leads to various human disorders. The first protein-misfolding disease was sickle cell anemia where, a single point mutation in the ?-globulin chain of hemoglobin changes from glutamic acid into a valine. But a major set of diseases is caused due to the formation of thread- like fibrillar aggregates from soluble proteins that are extremely resistant to protease degradation. These intractable aggregates accumulate extracellular and described as amyloid fibrils or plagues, while some amyloid form inside the cells and termed as intracellular inclusions. Till date, approximately 50 different proteinopathies has been identified. Originally, they were detected in Alzheimer’s (AD), Parkinson’s, Huntington’s and Creutzfeldt-Jakob’s diseases, but currently the list has been extended which include chronic hemodialysis, adult-onset diabetes, rheumatoid arthritis and inflammatory conditions. Primarily during aggregation, a small number of molecules associate and give rise to early aggregates that are rather unstable due to weak intermolecular interactions and can dissociate to produce soluble species. Though when aggregation advances, these stable oligomers structurally reorganize internally to well-defined fibrils having cross-? structure. It has been studied that conversion in ?-sheet structure is responsible for poor solubility and resistance to proteolysis. Alternatively, it has also been observed that these aggregates form large amorphous deposits or assemblies without any major structural re-organization and retains the structure of initial oligomers. All these types of large aggregates including amyloid, amorphous and native like assemblies accumulate in well defined pathological states and, thereby, associated with a wide range of human diseases as described in the Table 1. Characterization of each disease is based on a specific protein or polypeptide that aggregates into insoluble amyloid fibrils. Mostly the diseases caused due to these aggregates are associated with old age. Clinically amyloidosis are classified into primary, secondary, familial, and finally into isolated types.