Using a cross-sectional comparison group design, 4,746 ethnically diverse middle and high school students from 31 public schools in a metropolitan area were surveyed about their health, emotional factors (self-esteem, depressive symptoms, and suicidality), and behaviors (tobacco, alcohol, and drug use). Based on regression analyses that adjusted for gender, race, school level, and socioeconomic status, adolescents with chronic health conditions were significantly more likely to report depressive symptoms and low self-esteem than adolescents without chronic health conditions; they were almost twice as likely to have considered suicide and over 31/2 times more likely to have attempted suicide. They also reported greater use of cigarettes, marijuana, and illicit drugs. Given the extent of behavioral and emotional problems among adolescents with chronic health conditions, appropriate referrals and mental health services for these adolescents are warranted.