DNA replication is a complex mechanism that functions due to the co-ordinated interplay of several dozen protein factors. In the last few years, numerous studies suggested a tight implication of DNA replication factors in several DNA transaction events that maintain the integrity of the genome. Therefore, DNA replication fork proteins have also to be considered as part of a general process aiming at replicating and protecting the genome in order to allow the correct function of a cell and of its eventual daughter cells. This is illustrated by several DNA repair pathways such as base excision repair, nucleotide excision repair, double-strand break repair, and mismatch repair. Furthermore, several of the replication proteins have also been shown to be essential in sensing and transducing DNA damages through the checkpoint cascade pathways. This review will summarize the properties of DNA replication proteins that function exclusively at the replication fork.