Parthenium (Parthenium hysterophorus L.), the invasive weed of global significance, have a direct and indirect impact on human and animal health as well as the overall ecosystem health. Since its introduction to Ethiopia and the Tigray region, it rapidly covers millions of hectares of crop fields. Different biological control options were tested in many countries including Ethiopia, that ranging from fungus inoculation to the introduction of insect pests (bioagents) and two bioagents, the leaf-feeding beetle (Zygogramma bicolorata) and stem-boring weevil (Listronotus setosipennis) were reported to have better performance. Nevertheless, susceptibility of the bioagents to weather variability and predators were among the important factors that halts the effectiveness of the bioagent based biological control. In the Tigray region, the native pathogen, parthenium rust(Puccinia abrupta var. partheniicola) showed very promising effect against the noxious weed, parthenium, and proved to be reliable. In field condition, disease incidence that ranges between 20-100% was observed. As a result of the pathogenicity effect of the parthenium rust, symptoms like leaf and flower defoliation, chlorosis, necrosis, and stunted vegetative growth, and failure of seed production have been portrayed. The future use of uredospore suspensions of the parthenium rust as foliage application and as a mycoherbicide, and development of tolerant crop varieties via breeding are discussed.