Studies on the initiation of DNA replication in eukaryotes have progressed recently through different approaches that promise to converge. Proteins interacting with the origin recognition complex form a prereplicative complex early in the cell cycle. The regulation of the binding of MCM/P1 proteins to chromatin plays a key role in the replication licensing system which prevents re-replication in a single cell cycle. Cyclin-dependent kinases provide an overall control of the cell cycle by stimulating S-phase entry and possibly by preventing re-establishment of prereplicative complexes in G2 phase.