Panama disease is the most important lethal disease of banana. The causal soilborne fungus, Fusarium oxysporum f. sp. cubense (Foe), is found in most banana-producing regions and is pathologically and genetically diverse. Races of Foe, which affect different groups of cultivars, have been useful for describing host reactions and new disease outbreaks. Races 1 and 2 are heterogeneous, whereas populations of the pathogen that affect the Cavendish subgroup are more homogeneous; they are separated into subtropical race 4 (SR4), which causes damage only where cold winter temperatures occur, and tropical race 4 (TR4), which causes damage in the absence of predisposing conditions. TR4 is decimating Cavendish monocultures in southern Asia and would affect 85% of the global production of banana were it disseminated more widely. TR4's competence under tropical conditions and the wide range of cultivars that it affects make it a serious threat to export and small-holder production worldwide. This article summarizes the early history of, and research on, Panama disease, reviews its current status in different producing regions and recent research developments, and concludes with a discussion of TR4 diagnosis, interdiction, and control. Where TR4 has become established, it presents a most difficult management problem. There is an urgent need for innovative and useful research since the available management tactics are not very effective. If TR4 were to become established in the Western Hemisphere, radical changes would be needed in the American Cavendish-based export trades.