Enviromental or endogenous DNA damages of genomic DNA are either repaired by DNA repair mechanisms or lead apoptosis in living organisms. There are different DNA repair mechanisms such as direct DNA repair, nucleotide and base excision repair, recombinational repair. The most general and efficient repair mechanism known in living organisms is nucleotide excision repair pathway. Defects in nucleotide excision repair results in aging, carcinogenesis, various genetic and neurodegenerative disorders. Xeroderma pigmentosum, Cockayne syndrome and tricothiodystrophy are three rare hereditary disorders with nucleotide excision repair deficiency. Xeroderma pigmentosum is characterized with increased frequency of skin and internal organ cancers and in some case neurological abnormalities. These syndromes are very important to understand the molecular mechanisms of cancer and to design new therapeutic strategies. In normal population, interindividual variations in nucleotide excision repair capacity might be correlated with cancer proneness. Increased DNA repair capacity is also implicated in resistance of non-chirurgical cancer treatments.