Chromosome missegregation leads to aneuploidy which is defined as the cellular state of having a chromosome count that is not an exact multiple of the haploid number. Aneuploidy is associated with human diseases including mental retardation, neurodegenerative diseases and cancer. In addition, aneuploidy is the major cause of spontaneous abortions and its occurrence increases with aging. Therefore, it is important to understand the molecular mechanisms by which cells respond and adapt to aneuploidy. Saccharomyces cerevisiae has proven to be a good model to study the effects aneuploidy elicits on cellular homeostasis and physiology. This chapter focuses on the current understanding of how the yeast S. cerevisiae responds to the acquisition of extra chromosomes and highlights how studies in aneuploid yeasts provide insights onto the effects of aneuploidy in human cells.