Chromosome replication is not a uniform and continuous process. Replication forks can be slowed down or arrested by DNA secondary structures, specific protein-DNA complexes, specific DNA-RNA hybrids, or interactions between the replication and transcription machineries. Replication arrest has important implications for the topology of replication intermediates and can trigger homologous and illegitimate recombination. Thus, replication arrest may be a key factor in genome instability. Several examples of these phenomena are reviewed here.