Coffee is vital to the economy of East and Central Africa, providing a major source of foreign exchange earnings and, as a cash crop, supporting the livelihoods of millions involved in cultivation, processing, marketing, and export. Coffee wilt disease (CWD), attributed to Gibberella xylarioides (Fusarium xylarioides), has caused losses to coffee production in Africa since 1927 but has been largely contained through the use of host resistance and in some instances wide-scale sanitation practices. A reemergence of CWD on Coffea canephora (Robusta coffee) in Uganda, Democratic Republic of Congo, and Tanzania has already led to heavy losses and threatens future production in these countries and elsewhere in the region. The relevance of CWD is all the more pertinent given the impact of a considerable fall in world coffee prices over the last decade. Recent research has clarified the extent of the problem in the region and revealed a low level of diversity within the pathogen, suggesting that two genetically and biologically distinct forms are responsible for current problems. These findings and related research and development initiatives undertaken under the auspices of the Regional Coffee Wilt Programme are of fundamental importance in providing an urgently needed solution to this devastating disease.