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Screenings for genetic modifiers, such as suppressors or enhancers, in model organisms have identified and characterized important signaling pathways. Likewise, a phenotype induced by a chemical compound can be suppressed or enhanced by another compound. Here, I introduce chemical modifier screenings as phenotype-based assays that expand therapeutic targets to unexpected molecules and that facilitate identification of target signaling pathways. Also, chemical modifier screening can be applied to predicting possible drug-drug interactions that cause adverse effects.