Whole genome duplication (WGD) is an enormous mutation that doubles the DNA content in the nucleus. It has occurred in all eukaryotic lineages, and arises in somatic cells of multicellular plants as well as animals. WGD reshapes cellular geometry and physiology, and has important roles in development and stress resilience. It is also associated with aging and disease, and recognized as an engine of dangerous diversity in tumorigenesis. Here we discuss the adaptive potential and problems associated with WGD, focusing primarily on cellular effects and seeing polyploidy as a key player in cell lineage evolution, with strong parallels across kingdoms.