We present an overview of Gossypium genome evolution and the implications of this understanding for targeted breeding objectives. The cotton genus (Gossypium) contains more than 50 species distributed in arid to semiarid regions of the tropic and subtropics. Following the genus origin approximately 10–15 million years ago, a rapid global radiation leads to eight major genome groups (A through G and K) of diploids (n = 13). Allopolyploid cottons appeared within the last 1–2 million years, as a consequence of transoceanic dispersal of an A-genome taxon to the New World and subsequent hybridization with an indigenous D-genome diploid. The nascent allopolyploid radiated into three modern lineages of seven described species, including the agronomically important species G. hirsutum L. and G. barbadense L. These two allopolyploids, together with two A-genome diploids from Africa-Asia, G. arboreum L. and G. herbaceum L., were independently domesticated for their seed fiber, representing a remarkable case of human-driven parallel evolution. Recent investigations have clarified many aspects of this evolutionary history of Gossypium with genomic insights, including the paleopolyploid history of diploid species, a surprisingly high frequency of natural interspecific hybridization within and among genome groups, myriad interactions of molecular mechanisms underlying allopolyploid genome evolution, and a much-refined evolutionary relationship among gene pools of each of the four cultivated species. The extraordinary natural diversity in Gossypium in fiber morphology, stress tolerance, and other agronomic characteristics provides ample resources for breeders to develop new cotton varieties.