Although replication of different chromatin types is long known to occur at different times in the S phase, it was not until recently that the inheritance of replication timing came to be considered from the epigenetic viewpoint. Significant changes in genome replication timing are now known to occur during differentiation and are intimately linked with changes in transcriptional activity and nuclear architecture. Replication domains delineate discrete units of chromosome structure and function. The functional significance of this tight control of replication timing is not fully understood, but it is clear that replication program is a basic feature of a given differentiation state. The review focuses on the molecular mechanisms of spatial and temporal control of replication timing at the levels of both individual replication origins and extended chromatin domains.