Herbicide resistance is an important trait often introduced into crop plants. Mechanisms of resistance can involve a mutant target protein that is unaffected by the herbicide, or metabolic detoxification or degradation of the herbicide. Recently, we showed that overexpression in Arabidopsis thaliana of either psNTP9, the garden pea apyrase gene, or AtPgp1, the A. thaliana homolog of the plant multidrug resistance (MDR) gene, enabled A. thaliana to germinate on the toxin cycloheximide and to grow better on toxic levels of the plant hormone N6-[2-isopentyl]adenine (2iP). Here we report that overexpression of either MDR or apyrase proteins resulted in increased resistance to herbicides from different chemical classes. Apyrase inhibition by small molecule inhibitors reversed this resistance. Treatment of untransformed plants with an apyrase inhibitor increased their sensitivity to the same herbicides. These results indicate that the genes may be involved in a resistance mechanism relating to decreased retention or increased active efflux of herbicide from the plant cell.