It is argued in this lecture that in most eukaryotic cells onset of mitosis is coupled to attainment of a critical cell mass and to completion of the previous S-phase. In fission yeast these controls operate through a regulatory gene network that activates the p34cdc2 protein kinase at mitosis. This is brought about by dephosphorylation of a tyrosine residue located in the ATP binding site of the kinase. The p34cdc2 protein kinase is also important for regulating the onset of mitosis in vertebrate cells suggesting that there is a universal control regulating mitosis in all eukaryotic cells.