Escherichia coli can accurately replicate their genome even when it contains hundreds of damaged bases. In this situation, processes such as DNA repair, translesion DNA synthesis, and recombination all contribute to the cell's ability to successfully complete this task. However, under conditions when these reactions go awry, these same processes can result in cell lethality, mutagenesis, or genetic instability. In order to understand the molecular events that can lead this normally faithful duplication of the genome to become less than perfect, it is essential to define the substrates and conditions when each of these processes are recruited to the replication fork.