Trucking has been classified as one of the highest-risk occupations in the United States. Occupational stress is even greater for long-haul truckers who are away from home, family, friends, and other support networks for several days or weeks at a time. Occupational stressors and the mental health of truckers was studied using data collected as part of a large multisite ethno-epidemiological study of trucker networks. Findings from the current study show that truckers face many occupational stressors including constant time pressures, social isolation, disrespectful treatment from others, driving hazards such as weather changes, traffic, and road conditions, and violence or fear of violence. Facing such stressors may be a factor in the prevalence of risky behaviors including drug use and paying for sex. Therefore, mental health promotion and treatment for truckers is an important area of concern and must be examined within the broader context of the transportation environment.