Substance-related monitoring is an essential tool within environmental risk assessment processes. The soundness of policy decisions including risk management measures is often directly related to the reliability of the environmental monitoring programs. In addition, monitoring programs are required for identifying new and less-investigated pollutants of concern in different environmental media. Scientifically sound and feasible monitoring concepts strongly depend on the aim of the study. The proper definition of questions to be answered is thus of pivotal importance. Decisions on sample handling, storage and the analysis of the samples are important steps for the elaboration of problem-oriented monitoring strategies. The same applies to the selection of the sampling sites as being representative for scenarios to be investigated. These steps may become critical to handle for larger international monitoring programs and thus trigger the quality of their results. This study based on the work of an IUPAC (International Union of Pure and Applied Chemistry) task group addresses different kinds and approaches of substance-related monitoring of different compartments of soil, groundwater and surface water, and discusses their advantages and limitations. Further important aspects are the monitoring across policies and the monitoring data management using information systems.