Polyploidization, the addition of a complete set of chromosomes to the genome, represents one of the most dramatic mutations known to occur. Nevertheless, polyploidy is well tolerated in many groups of eukaryotes. Indeed, the majority of flowering plants and vertebrates have descended from polyploid ancestors. This Review examines the short-term effects of polyploidization on cell size, body size, genomic stability, and gene expression and the long-term effects on rates of evolution.