Polyploidy, or whole-genome duplication (WGD), is a ubiquitous feature of plant genomes, contributing to variation in both genome size and gene content. Although polyploidy has occurred in all major clades of land plants, it is most frequent in angiosperms. Following a WGD in the common ancestor of all extant angiosperms, a complex pattern of both ancient and recent polyploidy is evident across angiosperm phylogeny. In several cases, ancient WGDs are associated with increased rates of species diversification. For example, a WGD in the common ancestor of Asteraceae, the largest family of angiosperms with∼ 25 000 species, is statistically linked to a shift in species diversification; several other old WGDs are followed by increased diversification after a ‘lag’of up to three nodes. WGD may thus lead to a genomic combination that generates evolutionary novelty and may serve as a catalyst for diversification. In this paper, we explore possible links between WGD, the origin of novelty, and key innovations and propose a research path forward.