Cacao stands out as one of the major perennial crops in the world and is economically relevant as the source of chocolate, a multi-billion dollar product appreciated worldwide. Despite its importance, cacao is seriously affected by several diseases that reduce crop yields and decrease the quality of cocoa beans. Among them, the witches’ broom disease (WBD), caused by the basidiomycete Moniliophthora perniciosa, is the main constraint limiting cacao production in the Americas. Using next generation sequencing technologies, a comprehensive transcriptomic analysis of WBD was performed to investigate gene expression, structural variations (alternative splicing) and polymorphisms (SNPs) of both the pathogen and the plant. A total of 61 RNA-seq libraries were sequenced, including a wide range of developmental stages, growth conditions and stress responses of the fungus – either in vitro or in planta. Strikingly, a detailed analysis of genes expressed during the M. perniciosa-cacao interaction suggests the occurrence of remarkable physiological alterations in infected plants, which might culminate with the establishment of a senescence-like process in the host. Interestingly, the infected plant tissues seem to undergo carbon deprivation, as evidenced by repression of photosynthetic genes and induction of genes coding for amylases, lipases and glyoxysomal enzymes. Additionally, analysis of the pathogen transcriptome during cacao infection allowed the identification of potential pathogenicity factors, as well as the characterization of the metabolic status and infective strategy of M. perniciosa during WBD. A detailed molecular model of this particular plant-pathogen interaction will be presented.