The cell's euploid status is influenced by, amongst other mechanisms, an intact spindle assembly checkpoint (SAC), an accurate centrosome cycle, and proper cytokinesis. Studies in mammalian cells suggest that dysregulated SAC function, centrosome cycle, and cytokinesis can all contribute significantly to aneuploidy. Of interest, human cancers are frequently aneuploid and show altered expression in SAC genes. The SAC is a multi-protein complex that monitors against mis-segregation of sister chromatids. Several recent experimental mouse models have suggested a link between weakened SAC and in vivo tumorigenesis. Here, we review in brief some mechanisms which contribute to cellular aneuploidy and offer a perspective on the relationship between aneuploidy and human cancers. J. Cell. Biochem. 102: 531–538, 2007. © 2007 Wiley-Liss, Inc.