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Detoxification is a coordinated defense rather than a single reaction. Phase I enzymes, including CYP450s, flavin monooxygenases, and epoxide hydrolase, modify xenobiotics and may produce reactive intermediates. Phase II conjugations increase water solubility, while Phase III transporters promote efflux. Cellular protection also relies on glutathione and antioxidant systems that counter electrophiles and reactive oxygen species. NRF2-KEAP1 and xenobiotic-sensing receptors regulate genes involved in detoxification and defense. Additional mechanisms include metal binding by metallothioneins, aldehyde processing by aldehyde dehydrogenase, organophosphate hydrolysis by PON1, thioredoxin-mediated redox control, and protein quality control by heat-shock proteins. Together, these systems reduce exposure to harmful compounds and help limit cellular injury.