Considered a biodiversity hotspot, the Canary Islands have been the key subjects of numerous evolutionary studies concerning a large variety of organisms. The genus Cheirolophus (Asteraceae) represents one of the largest plant radiations in the Canarian archipelago. In contrast, only a few species occur in the Mediterranean region, the putative ancestral area of the genus. Here, our main aim was to reconstruct the phylogenetic and biogeographic history of Cheirolophus with special focus on explaining the origin of the large Canarian radiation. Results: We found significant incongruence in phylogenetic relationships between nuclear and plastid markers. Each dataset provided resolution at different levels in Cheirolophus: the nuclear markers resolved the backbone of the phylogeny while the plastid data provided better resolution within the Canarian clade. The origin of Cheirolophus was dated in the Mid-Late Miocene, followed by rapid diversification into the three main Mediterranean lineages and the Macaronesian clade. A decrease in diversification rates was inferred at the end of the Miocene, with a new increase in the Late Pliocene concurrent with the onset of the Mediterranean climate. Diversification within the Macaronesian clade started in the Early-Mid Pleistocene, with unusually high speciation rates giving rise to the extant insular diversity. Conclusions: Climate-driven diversification likely explains the early evolutionary history of Cheirolophus in the Mediterranean region. It appears that the exceptionally high diversification rate in the Canarian clade was mainly driven by allopatric speciation (including intra-and interisland diversification). Several intrinsic (e.g. breeding system, polyploid origin, seed dispersal syndrome) and extrinsic (e.g. fragmented landscape, isolated habitats, climatic and geological changes) factors probably contributed to the progressive differentiation of populations resulting in numerous microendemisms. Finally, hybridization events and emerging ecological adaptation may have also reinforced the diversification process.