DNA mismatch repair is the process of fixing errors that arise in the genome during DNA replication and recombination. This is accomplished by the recognition of DNA lesions and the subsequent recruitment of factors to remove the damaged DNA and then incorporate the correct DNA sequence. The faithful maintenance of the genomic sequence is important since the accumulation of somatic mutations can disrupt basic processes within a cell and the accumulation of germline mutations can lead to inherited mutations or even inviable daughter cells. Errors in basic repair processes have severe consequences for stability of the genome and the development of cancer. Disruption of mismatch repair genes themselves leads to an overall defect in DNA mismatch repair causing the genome to accumulate mutations at a high rate. This hypermutation phenotype will eventually cause mutations at gene loci important for regulating the cell cycle and therefore lead to tumor development. A variety of studies presented here, demonstrate the importance of a functional mismatch repair system in the cell and provide a detailed analysis of mismatch recognition by the Msh2-Msh3 complex