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Rehabilitation of downy brome–infested shrublands is challenging once this invasive grass dominates native communities. The effectiveness of imazapic herbicide in reducing downy brome cover has been variable, and there is uncertainty about the impacts of imazapic on native species. We used a before-after-control-impact (BACI) field experiment and greenhouse studies to (1) determine if imazapic herbicide applied at 132 g ai ha−1 (8 oz/ac−1) and seeding with two native shrub species (Wyoming big sagebrush [Artemisia tridentata] and Mexican cliffrose [Purshia mexicana]) reduced downy brome cover and promoted shrub establishment, (2) assess potential effects of imazapic on nontarget plant species and plant community composition, and (3) determine if imazapic affected downy brome or seeded shrub species when applied at different developmental stages. Seeding shrubs, alone, or in combination with imazapic application, did not significantly increase shrub density, possibly because of droughty conditions. In the field, imazapic reduced downy brome cover by 20% and nontarget forb cover by 25% and altered plant community composition the first year after treatment. Imazapic was lethal to downy brome at all growth stages in the greenhouse and reduced shrub germination by 50 to 80%, but older shrub seedlings were more tolerant of the herbicide. We conclude that a one-time application of imazapic combined with seeding shrubs was only slightly effective in rehabilitating areas with high downy brome and thatch cover and resulted in short-term impacts to nontarget species. These results highlight the need to treat downy brome infestations before they become too large. Also, removing thatch prior to treating with imazapic, although likely lethal to the native shrubs we studied, could increase the effectiveness of imazapic.