The genus Helichrysum has 500-600 species in Africa, Madagascar, the Mediterranean basin, Macaronesia, western and central Asia, and India. The aims of this study are to confirm the exclusion of Castroviejoa from Helichrysum, to elucidate the origin of the Macaronesian endemics, to confirm the monophyly of the Mediterranean-Asiatic group, and, within this group, to contrast molecular data with sectional classification and to provide insight into trends in character evolution and biogeography. To address these issues, ITS and ETS sequences were used in phylogenetic analyses. Results show that Castroviejoa is excluded from Helichrysum. The phylogeny obtained suggests a southern African origin for Helichrysum and several subsequent migrations throughout the African continent. The species from the Canary Islands do not form a monophyletic clade, suggesting that at least two independent colonization events occurred. Helichrysum makranicum, from Oman and southern Iran, is the closest relative of a clade consisting of two endemics of the Canary Islands, providing new evidence of the phytogeographical links between Macaronesia and eastern Africa-southern Arabia. Helichrysum gossypinum, the third endemic of the Canary Islands, is the sister species of a monophyletic Mediterranean and Asiatic group, with the four endemics of Madeira sister to all of them. Within the Mediterranean-Asiatic clade, sect. Stoechadina is monophyletic, but sect. Helichrysum and sect. Virginea are not. Once in the Mediterranean region, the genus is hypothesized to have diversified and expanded to the east up to western and central Asia and to have suffered a reduction in woodiness.