Base damage or loss occurs at high frequency in the cells (almost 10(4) bases are damaged and hydrolysed per cell per day). DNA repair is fundamental to maintain genomic integrity. Base excision repair (BER) is the main mechanism by which cells correct various types of damaged DNA bases generated either by endogenous or exogenous factors. The widely accepted model for BER mechanism involves five sequential reactions: (i) base removal; (ii) incision of the resulting abasic site; (iii) processing of the generated termini at the strand break; (iv) DNA synthesis, and (v) ligation. In this review, we will briefly summarise the biochemistry of each BER step and will concentrate on the biological relevance of BER as inferred from in vitro and in vivo studies. This information will be the basis for speculation on the potential role of malfunction of BER in human pathology.