Some protective responses can be activated to be against toxicity of stresses and pollutants. We here discussed the role of protective responses–related signals as the “effectors” for formation of transgenerational toxicity induced by stresses and pollutants. We first introduced the transgenerational oxidation response, mitochondrial unfolded protein response (mt UPR), endoplasmic reticulum unfolded protein response (ER UPR), and innate immune response to pollutants. Moreover, we introduced and discussed the molecular basis for induction of transgenerational oxidation response, mt UPR response, and innate immune response to pollutants.