The modifying effects of psychiatric and familial risk factors on age at smoking initiation, rate of progression from first cigarette to regular smoking, and transition time from regular smoking to nicotine dependence (ND) were examined in 1269 offspring of male twins from the Vietnam Era Twin Registry. Mean age of the sample was 20.1 years. Cox proportional hazard regression analyses adjusting for paternal alcohol dependence and ND status and maternal ND were conducted. Both early age at first cigarette and rapid transition from initiation to regular smoking were associated with externalizing disorders, alcohol consumption, and cannabis use. Rapid escalation from regular smoking to ND was also predicted by externalizing disorders, but in contrast to earlier transitions, revealed a strong association with internalizing disorders and no significant relationship with use of other substances. Findings characterize a rarely examined aspect of the course of ND development and highlight critical distinctions in risk profiles across stages of tobacco involvement.