This chapter provides a comprehensive review of the pharmacology of nicotine, focusing on its absorption, distribution, metabolism, and excretion. Nicotine, a key component of tobacco products, is primarily metabolized by liver enzymes CYP2A6, UDP-glucuronosyltransferase (UGT), and flavin-containing monooxygenase (FMO). The metabolism of nicotine is influenced by various factors, including genetic variations, diet, age, sex, hormonal status, and smoking behavior. Cotinine, the primary biomarker of nicotine intake, is measured in blood, urine, saliva, hair, or nails, with a plasma cut-point of 3 ng/ml to distinguish smokers from non-smokers. The chapter also discusses the distribution of nicotine in body tissues, the renal excretion of nicotine and its metabolites, and the impact of smoking on nicotine metabolism. Additionally, it explores racial and ethnic differences in nicotine metabolism and the role of medications and smoking in influencing nicotine clearance. The chapter highlights the importance of understanding these pharmacological aspects for developing effective smoking cessation interventions.This chapter provides a comprehensive review of the pharmacology of nicotine, focusing on its absorption, distribution, metabolism, and excretion. Nicotine, a key component of tobacco products, is primarily metabolized by liver enzymes CYP2A6, UDP-glucuronosyltransferase (UGT), and flavin-containing monooxygenase (FMO). The metabolism of nicotine is influenced by various factors, including genetic variations, diet, age, sex, hormonal status, and smoking behavior. Cotinine, the primary biomarker of nicotine intake, is measured in blood, urine, saliva, hair, or nails, with a plasma cut-point of 3 ng/ml to distinguish smokers from non-smokers. The chapter also discusses the distribution of nicotine in body tissues, the renal excretion of nicotine and its metabolites, and the impact of smoking on nicotine metabolism. Additionally, it explores racial and ethnic differences in nicotine metabolism and the role of medications and smoking in influencing nicotine clearance. The chapter highlights the importance of understanding these pharmacological aspects for developing effective smoking cessation interventions.