CYP2B6 is a microsomal cytochrome P450 enzyme that catalyzes the oxidative metabolism of multiple clinically important drugs and xenobiotics. The enzyme displays broad substrate selectivity and acts as both a monooxygenase and epoxygenase, metabolizing substrates including anandamide, steroids, and arachidonate 1. CYP2B6 represents the only functional member of the human CYP2B gene subfamily, localized to chromosome 19–19q13.2, and undergoes complex alternative splicing that generates both functional and non-functional transcripts 2. Clinically, CYP2B6 genetic variation substantially affects the metabolism and efficacy of several therapeutically important drugs 3. Polymorphisms impact efavirenz (HIV treatment), methadone (opioid use disorder and analgesia), ketamine (antidepressant and analgesic), and bupropion (depression and smoking cessation) 3. The enzyme also metabolizes cyclophosphamide and ifosfamide, where CYP2B6 catalyzes major activation pathways 1. Recent evidence suggests carbamazepine, at therapeutic serum concentrations, is genotoxic in a CYP2B6-dependent manner, inducing clastogenesis and gene mutations through selective CYP2B6-mediated bioactivation 4. Additionally, CYP2B6 expression is significantly elevated in HIV/HCV co-infected patients 5, potentially influencing antiretroviral pharmacokinetics. Ticlopidine and clopidogrel are potent mechanism-based inhibitors of CYP2B6 6, highlighting clinically relevant drug–drug interaction potential with CYP2B6 substrates.