Background: This study provides a descriptive profile of substance use behavior and the prevalence of suicide indicators (thought about, considered, and planned) among rural middle school students and examines the association between substance use and suicidal indicators among middle school students participating in the Coordinated School Health Program in a rural state. Methods: During April and May 2004, 10,273 middle school students completed the middle school Youth Risk Behavior Survey. Results: This study found that a large percentage of students had initiated substance use behavior, with the greatest number of students having tried cigarettes (40.9% females and 42.7% males), followed by alcohol use (37.2% females and 41.3% males). Additionally, suicidal ideation and behavior were prevalent. Significant associations were found between substance use and suicidal ideation and behavior among middle school students. Conclusions: Prevention programs for adolescent suicide should be implemented during the middle school years and should focus on preventing substance use given its relationship to suicide. (Contains 5 tables.)