We are exposed to a variety of electrophiles such as aromatic hydrocarbon quinones formed during combustion of gasoline, crotonaldehyde in tobacco smoke, methylmercury accumulated in fish, cadmium contaminated in rice, and acrylamide in baked foods on a daily basis, and the molecular target for these electrophiles in the body are macromolecule nucleophiles. There are various redox signaling pathways consisting of sensor proteins with reactive cysteine residues and effector molecules (e.g., kinase and transcription factor) in cells, and the effector molecules are negatively regulated by the sensor proteins in basal condition. We found that environmental electrophiles selectively and covalently modify sensor proteins such as protein tyrosine phosphatase 1B (PTP1B), kelch-like ECH-associated protein 1 (Keap1), heat shock protein 90 (HSP90) and phosphatase and tensin homolog deleted from chromosome 10 (PTEN), resulting in inhibition of their activities at lower concentrations, thereby activating effector molecules such as epidermal growth factor receptor (EGFR), NF-E2-related factor 2 (Nrf2), heat shock factor 1 (HSF1) and protein kinase B (Akt). However, activated redox signaling pathways are disrupted by environmental electrophiles at higher concentrations due to nonselective and extensive modification of cellular proteins, leading to cellular toxicity. We therefore suggest that electrophiles have two different aspects in term of redox signaling pathways.