The evolution of karyotypes has been the subject of intensive study since the middle of the 20th century. This was motivated by the observation that the karyotypes of related species showed remarkable conservation. The recent emergence of whole-genome sequencing projects gives the opportunity to complement the cytogenetic approaches by addressing the conservation of karyotypes using chromosome sequence comparison. In this short review we present a description of recent advances in computational biology methods dedicated to the study of chromosome evolution and more specifically ancestral karyotype reconstruction in an attempt to provide an integrated overview of both cytogenetic and computational approaches.