The introduction of the European Commission's Water Framework Directive (WFD; 2000/60/EC) established a new era in environmental risk assessment. In addition to incorporating the compliance of chemical quality standards, the key objective of the WFD is the general protection of the aquatic environment in its entirety. This new approach emphasizes the need for an integrated environmental risk assessment and offers the potential for the incorporation of biological effects measures, including the use of biomarkers in this process. Biomarkers have been suggested as practical tools for environmental management for a number of decades, but their inclusion has not been universally accepted because of a number of unanswered questions regarding sensitivity, practicality, and reproducibility. With this in mind, this paper addresses these potential questions and shows how, by taking a weight-of-evidence approach, biomarkers may be successfully incorporated within environmental risk assessment frameworks such as the WFD.