Tobacco use leads in short time to nicotine dependence. Mechanisms of this process remain still not quite understood, of importance is also a question: When does nicotine dependence begin? The present review reports commonly used definition of nicotine dependence (according to Diagnostic and Statistical Manual of Mental Disorders Fourth Edition and International Statistical Classification of Diseases and Health Related Problems Tenth Revision), as well as its limited value in detecting first symptoms of this process. The review presents also the concept, which links the beginning of dependence with diminished autonomy (i.e., autonomy theory), results of studies supporting this concept, and neurophysiologic model of sensitization-homeostasis for nicotine dependence development. Further, despite phenomenon of sensitization has not been demonstrated in humans, results of animal studies arguing for sensitization-homeostasis theory are presented in the article. Usefulness of the Hooked on Nicotine Checklist in diagnosing first nicotine dependence symptoms in adolescents is also pointed out.