This review will describe the biological and behavioral aspects of nicotine addiction as it develops during adolescence and advances over a lifetime. Symptoms of physical nicotine dependence typically appear when adolescents are smoking only a few cigarettes each month. Physical dependence develops through a set sequence of symptoms that correlate with changes in brain structure in addiction circuits. Smokers often describe their symptoms of physical dependence as “wanting,” then “craving,” and eventually “needing” to smoke. These symptoms appear whenever the smoker goes too long without smoking. The intensity of abstinence-induced craving correlates with spontaneous activation of addiction-related networks in the brain as illustrated in the graphical abstract of this article. Initially, smoking a single cigarette can keep withdrawal symptoms at bay for weeks, but as tolerance develops, cigarettes must be smoked at progressively shorter intervals to suppress withdrawal symptoms. The physiologic need to repeatedly self-administer nicotine at shorter intervals explains a full spectrum of addictive symptoms and behaviors.