The MCM proteins are essential replication initiation factors originally identified as proteins required for minichromosome maintenance in Saccharomyces cerevisiae. The best known among them are a family of six structurally related proteins, MCM2–7, which are evolutionally conserved in all eukaryotes. The MCM2–7 proteins form a hexameric complex. This complex is a key component of the prereplication complex that assembles at replication origins during early G1 phase. New evidence suggests that the MCM2–7 proteins may be involved not only in the initiation but also in the elongation of DNA replication. Orchestration of the functional interactions between the MCM2–7 proteins and other components of the prereplication complex by cell cycle–dependent protein kinases results in initiation of DNA synthesis once every cell cycle.