A number of checkpoint controls function to preserve the genome by restraining cell cycle progression until prerequisite events have been properly completed. Chromosome attachment to the mitotic spindle is monitored by the spindle assembly checkpoint. Sister chromatid separation in anaphase is initiated only once all chromosomes have been attached to both poles of the spindle. Premature separation of sister chromatids leads to the loss or gain of chromosomes in daughter cells (aneuploidy), a prevalent form of genetic instability of human cancer. The spindle assembly checkpoint ensures that cells with misaligned chromosomes do not exit mitosis and divide to form aneuploid cells. A number of protein kinases and checkpoint phosphoproteins are required for the function of the spindle assembly checkpoint. This review discusses the recent progress in understanding the role of protein kinases of the mitotic checkpoint complex in the surveillance pathway of the checkpoint.