The fungal genus Colletotrichum (sexual stage: Glomerella) (Glomerellaceae) is one of the most common and destructive groups of plant pathogenic fungi, causing disease on plants from nearly every crop and natural ecosystem worldwide. Several closely related Colletotrichum species are associated with grass and cereal hosts as destructive pathogens, causing disease in crops grown for food, fuel, and fiber, and in plants inhabiting natural landscapes. Colletotrichum diseases can negatively impact many of the most important monocots targeted for use as candidate bioenergy crops, including switchgrass, miscanthus, maize, sorghum, indiangrass, and sugarcane. Many grass-associated Colletotrichum are ubiquitous endophytic components of the foliar microbiome. As such, grass-infecting fungi in the genus Colletotrichum present a unique model system in which to investigate overlapping themes of host-specialization, endophytism and pathogenicity within the context of their impact on bioenergy and food producing crops. Knowledge gained from comparative genomic research of these fungi will provide valuable insight into the molecular basis of pathogenicity, cellulosic biomass degradation and other traits that characterize this diverse group of grass pathogens.