Substance flow analysis (SFA) has been used by the Danish Environmental Protection Agency for more than two decades to identify sources of hazardous substance releases to the environment and to waste streams. More than 35 SFAs have been undertaken using a unified methodology. This article discusses key elements of the methodology and application of the results of the SFAs in Denmark, illustrated by examples. The use of repeated SFAs in the evolution of substance regulation is demonstrated for lead. A cadmium SFA illustrates the use of SFAs to monitor changes in consumption and release of a hazardous substance. Estimates of sources are presented for a number of toxic and resource‐intensive metals in solid waste incineration and sewage treatment. Most of the SFAs concern hazardous substances, but aluminum represents a case in which the resource perspective is an important element in a national SFA. The Danish SFA on brominated flame retardants illustrates some methodological problems with conducting national SFAs in a global economy in which the substances are mainly imported in finished products.