Data from the Canadian Youth Smoking Survey (n = 27,030 in 2006; n = 16,705 in 2004; n = 11,757 in 2002) were used to examine changes in the prevalence and comorbid use of alcohol, tobacco, and marijuana over time and examine if demographic factors and binge drinking are associated with comorbid substance use among youth. Alcohol was the most prevalent substance used, and it was rare to find youth who had used tobacco or marijuana without also having tried alcohol. Youth who reported binge drinking were substantially more likely to also have tried tobacco and/or marijuana. These data suggest that multi-substance prevention programs are required for youth populations.