Abstract: The invention provides methods and reagents for identifying compounds that exhibit anti-nematode activity and compounds that potentiate the effects of other anti-nematode agents. The invention provides methods identifying modulators of nematode xenobiotic sensing nuclear receptors. The invention also provides methods for screening for anti-nematode compounds using sensitized nematode strains and further provides such sensitized strains. The invention further provides methods and screens for identifying new biological targets for anti-nematode compounds, e.g., for identifying nematode genes and proteins towards which anti-nematode compounds can be developed. The invention provides methods for controlling parasitic nematodes using compounds identified in the inventive screens. In addition, the invention provides sensitized nematode strains and methods for using such strains to enhance identification of compounds in the context of a wide variety of nematode model screening systems and strains.