Molecular pathology of forest trees for a long time lagged behind parallel studies on agricultural crop pathology. Recent technological advances have significantly contributed to the observed progress in this field. The first powerful impulse was provided by the completion of the black cottonwood genome sequence in 2006. Genomes of several other important tree species will be completed within a short time. Simultaneously, application of transcriptomics and next-generation sequencing (NGS) has resulted in the rapid accumulation of a vast amount of data on molecular interactions between trees and their microbial parasites. This review provides an overview of our current knowledge about these responses of forest trees to their pathogens, highlighting the achievements of the past decade, discussing the current state of the field, and emphasizing the prospects and challenges for the near future.