Disrupted passage through mitosis often leads to chromosome missegregation and the production of aneuploid progeny. Aneuploidy has long been recognized as a frequent characteristic of cancer cells and a possible cause of tumorigenesis. Drugs that target mitotic spindle assembly are frequently used to treat various types of human tumors. These lead to chronic mitotic arrest from sustained activation of the mitotic checkpoint. Here, we review the linkage between the mitotic checkpoint, aneuploidy, adaptation from mitotic arrest, and antimitotic drug-induced cell death.