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Whole genome duplication (WGD) occurs in all kingdoms and can aid adaptation. But early on, WGD is traumatic to the cell, and often fatal. In autopolyploids (within-species WGD), many processes must adapt to the new cellular landscape. We showed that DNA repair and cell division can nimbly shift, allowing natural polyploids to survive, but what explains the bigger question: how do some polyploids thrive? I suggest that the very challenges that WGD brings provide a hint: these processes control the generation of genomic structural variation. Here I suggest that the post-WGD shakeup—the stumbling process of adaptation to WGD—is itself a generative engine for evolutionary success. That is, WGD-mediated success may arise from early maladaptation to the very same challenges WGD brings. We are now testing mechanisms: in particular, if repair and division errors and centromere/kinetochore coevolution are key missing pieces in the century-long quest to understand polyploid adaptation.