The DNA damage and replication checkpoints are signaling mechanisms that regulate and coordinate cellular responses to genotoxic conditions. The activation of checkpoints not only attenuates cell cycle progression, but also facilitates DNA repair and recovery of faulty replication forks, thereby preventing DNA lesions from being converted to inheritable mutations. It has become increasingly clear that the activation and signaling of the checkpoint are intimately linked to the cellular processes directly involved in chromosomal metabolism, such as DNA replication and DNA repair. Thus, the checkpoint pathway is not just a surveillance system that monitors genomic integrity and regulates cell proliferation, but also an integral part of the processes that work directly on chromosomes to maintain genomic stability. In this article, we discuss the current models of DNA damage and replication checkpoints, and highlight recent advances in the field.