Identifying the factors related to the initiation and continuance of smoking among youth has been regarded as a crucial step for school nurses and public health nurses to develop effective smoking prevention and cessation programs in schools and communities. The purpose of this study was to investigate the factors related to adolescent tobacco use in southern Taiwan. A total of 4,500 study samples were selected at random from the students of all high schools located in Pingdong County. This process yielded 3,307 valid samples (a 73.5% response rate). Study results found 62.4% (n = 2,063) reported never having smoked before. Thirty-eight percent (n = 1,244) of participants had experience using tobacco, 59.3% (n = 738) reported being ex-smokers, and 40.7% (n = 506) were current smokers. This study found that having friends who offered cigarettes, academic achievement, father's educational level, perceived peer smoking behavior to be primary influences on smoking, attitude, and self-efficacy and significant predicators of adolescents' current smoking behaviors. Parents' marital status and having classmate who offered cigarettes were significant predictors of adolescent smoking behavior. Study findings can provide a basis for school and public health nurses to design effective smoking prevention and cessation programs in schools and community settings. This study suggests further experimental studies are necessary to test the effectiveness of tobacco control programs designed in reference to the findings of this study.