Introduction: This contribution gives an overview on estimating the economic impact of substance use (SU) and substance use disorders (SUDs) from a societal perspective. Areas covered: In this Expert Review, we first discuss the scope of the economic costs of SU to society and the methods used to estimate them. In general, cost studies should not be limited to SUDs, but should also include costs related to the consequences of any type of SU to achieve a comprehensive picture of the societal burden. Further, estimating potentially avoidable costs will increase the value of cost studies. Importantly, methodologically sound cost studies shed light on the magnitude of societal problems related to SU and can be used as a reference point to evaluate regulatory policies and other preventive measures. The area of estimating potential economic benefits of SU is understudied and lacks a theoretical and methodological framework. Expert opinion: Overall, economic studies on the impact of SU and SUDs can strongly contribute to better-informed decision-making in the creation of regulatory and control policies. The least developed area of research refers to a consensus methodology that could be used in studies which compare economic costs to potential economic benefits.