Numerous external and internal DNA damaging agents can affect genetic material to produce single-strand breaks (SSB), double strand breaks (DSB), interand intra-strand cross-links in the form of cyclobutane pyrimidine dimers and (6-4)-photoproducts, oxidation and alkylation of bases, or formation of bulky chemical adducts. Cells possess several biological processes that act in a coordinated way to supervise DNA molecules and properly repair DNA lesions to minimize genetic information loss. This DNA repair system, which has been conserved throughout eukaryotes and prokaryotes evolution, includes various pathways that can be classified according to the type of DNA lesion they can restore: i) DSB, the most detrimental lesions of DNA, can be repaired by homologous recombination (HRR) and non-homologous end joining (NHEJ) pathways [Fleck & Nielsen, 2004]; ii) aberrant bases or nucleotides from a single strand DNA can be repaired by base excision repair (BER), nucleotide excision repair (NER) and mismatch repair (MMR) pathways using the complementary strand as template for DNA synthesis. BER mainly restores non-bulky lesions that result from bases alkylation, oxidation or deamination [Krokan et al., 1997]. The main task of NER pathway, which consists in two subpathways: global genome repair (GGR) to remove damage in the overall genome and transcription-coupled repair (TCR) to specifically repair the transcribed strand of active genes, is to eliminate photoproducts produced by ultraviolet (UV) light and other bulky lesions, such as interand intra-strand crosslinks [Prakash &Prakash, 2000]. MMR allows the removal of base mismatches and small insertion/deletion loops (IDL) that are formed during the replication process [Marti et al., 2002]. The genome of protozoan parasites is continuously subjected to the effects of antiparasitic drugs and host immune system attacks, which can affect its stability and therefore parasite survival. Thus, efficient DNA maintenance mechanisms are necessary to detect and accurately repair damaged nucleotides. The fully sequenced genome of the four major human pathogens described here provides new insights into parasite biology, including molecular features of