Soybean stem canker (SSC) is an important disease caused by different Diaporthe spp., including D. aspalathi, D. caulivora and D. longicolla, that leads to soybean (Glycine max) yield losses around the world. Most studies have been focused on the morphological characterization and molecular identification of Diaporthe spp. present in SSC lesions. Several soybean resistance loci to Diaporthe spp. causing SSC have been identified, although the molecular identities of the resistance genes are at present unknown. In this review, we summarize the current knowledge on SSC disease, the molecular characterization of Diaporthe spp.and their evolutionary relationships. We highlight how recent genomic and transcriptomic information is allowing significant progress in our understanding of the molecular components and mechanisms underlying Diaporthe infection strategies as well as soybean disease resistance. The information generated, combined with available resources enabling functional genomics, will contribute to the development of breeding strategies for disease resistance, leading to a more sustainable agriculture.