Polyploidy is one of the major evolutionary forces in plants and in particular in the largest angiosperm family, the Asteraceae. This chromosome set multiplication directly impacts the nuclear DNA contents, in terms of variation at holoploid and monoploid levels. Other karyological changes such as aneuploidy or dysploidy might produce genome size alterations as well, therefore playing also a relevant role as evolutionary forces. All these factors may promote speciation, thus having systematic implications. In this paper we review the mechanisms associated with genome size variation, as well as their evolutionary consequences at phylogenetic, systematic and even taxonomic levels. To do so, C–values and chromosome numbers have been compiled and complemented with other molecular cytogenetic data to be discussed within their respective molecular phylogenetic frameworks. The case studies come from several genera of the Asteraceae belonging to tribes Anthemideae (Artemisia) and Cardueae (Cheirolophus, Echinops and members of Rhaponticum group), which cover a wide range of life strategies (e.g., life cycles, ecology, geographical distribution).