Fatal yellowing disease (FY) is a bud rot-type disease that severely affects oil palm plantations in Latin America. Since 1974, when it was first reported in Brazil, this disorder has been responsible for severe economic losses in the oil palm industry; and, for nearly 50 years, several studies have tried to identify its causal agent, without success. The etiological studies regarding FY in oil palm explored either biotic and abiotic stress scenarios, in a single or combined manner. Most recently, the hypothesis in favor of one biotic cause has lost some grounds to the abiotic one, mainly due to new insights regarding deficient aeration in the soil, which reduces the potential for oxy-reduction, causing changes in the ionic composition of the soil solution. This review presents an overview of the history of this disease and the several efforts done to fulfill Koch’s postulates over the last 40 years, besides discussing recent studies that revisited this subject using some omics technics. We conclude by discussing further uses of omics via a multi-omics integration (MOI) strategy to help finally find out what is really behind the genesis of FY. Finding this elusive causal agent of FY out will allow either the development of a more efficient diagnostic tool and the advance in studies trying to find out the source of the genetic resistance hidden in the genome of the American oil palm.

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