Defects in DNA-repair pathways lead to an accumulation of mutations in genomic DNA that result from non-repair or mis-repair of modifications introduced into the DNA by endogenous or exogenous agents or by the malfunction of DNA metabolic pathways. Until recently, only two repair pathways, postreplicative mismatch repair and nucleotide excision repair, have been linked to cancer in mammals, but these have been joined in recent months also by the damage-reversal and base-excision-repair processes, which have been shown to be inactivated, either through mutation or epigenetically, in human cancer.