The abundance of polyploidy among flowering plants has long been recognized, and recent studies have uncovered multiple ancient polyploidization events in the evolutionary history of several angiosperm lineages. Once polyploids are formed they must get locally established and then propagate and survive while adapting to different environments and avoiding extinction. This might ultimately lead to their long-term evolutionary success, where their descendant lineages survive for tens of millions of years. Along this road to evolutionary success, polyploids must overcome several obstacles, to which several genetic and ecological factors are likely to contribute. One recurrent observation, based on present-day polyploids, has been the high frequency of polyploids in harsh environments. Also, recent studies proposed that the success of certain ancient polyploids might be linked to periods of climatic change. Although we are still in the early stages of unraveling the factors that resulted in the long-term evolutionary success of ancient polyploids, the advances in genomic sequencing and molecular dating methods promise to enhance our understanding. It, therefore, seems timely to review our current knowledge of what determines the success of polyploids. Here, we discuss especially how harsh conditions or periods of climatic change might affect the rate of formation, establishment, persistence and long-term evolutionary success of polyploids in angiosperms.