This special journal issue, Exploring substance use in Canada: Trends and emerging issues in public health, comes at a critical time for Canadian health policy makers and researchers. Most attention is currently focussed on the opioid crisis and the potential impacts of cannabis legalization. However, our most widely used and harmful substances continue to be alcohol and nicotine. Our policies to reduce harms from these substances are failing. While alcohol control policies are being gradually abandoned, opportunities to maximize the harm reduction potential of new, alternative and safer nicotine delivery devices are not being grasped. More generally, a greater focus is needed on harm reduction strategies that are informed by the experience of marginalized people with severe substance use-related problems so as to not exacerbate health inequities. In order to better inform policy responses, we recommend innovative approaches to monitoring and surveillance that maximize the use of multiple data sources, such as those used in the Canadian Substance Use Costs and Harms (CSUCH) project. Greater attention to precision in defining patterns of risky use and harms is also needed to support policies that more accurately reflect and respond to actual levels of substance use-related harm in Canadian society.