This review article focuses on protein kinases regulating the onset and transition through mitosis. The essay begins by introducing the structural features of the protein kinase catalytic domain and emphasizing the mechanism of enzymatic activation of this class of proteins. Next follows a short historical perspective on cell division and a description of our current understanding of mitosis. In the central part of the review I examine the four major kinases that set the stage for mitosis, which consist of Cdk1, Polo-like 1, Nek2 and Aurora kinases. For each entry dealt with, I focus particularly on studies that have linked DNA damage response pathways to inhibition of kinase activity, and I evaluate the conclusions drawn. Finally, I examine protein kinases initially described in the context of different cell cycle transitions and only later proposed to be involved in the control of mitosis.