Determination of the level of exposure during and after a chemical incident is crucial for the assessment of public health risks and for appropriate medical treatment, as well as for subsequent health studies that may be part of disaster management. Immediately after such an incident, there is usually no opportunity to collect reliable quantitative information on personal exposures and environmental concentrations may fall below detectable levels shortly after the incident has passed. However, many substances persist longer in biological tissues and thus biological monitoring strategies may have the potential to support exposure assessment, as part of health studies, even after the acute phase of a chemical incident is over. Reported successful applications involve very persistent chemical substances such as protein adducts and include those rare cases in which biological tissues were collected within a few hours after an incident. The persistence of a biomarker in biological tissues, the mechanism of toxicity, and the sensitivity of the analysis of a biomarker were identified as the key parameters to support a decision on the feasibility and usefulness of biological monitoring to be applied after an incident involving the release of hazardous chemicals. These input parameters could be retrieved from published methods on applications of biomarkers. Methods for rapid decision making on the usefulness and feasibility of using biological monitoring are needed. In this contribution, a stepwise procedure for taking such a decision is proposed. The persistence of a biomarker in biological tissues, the mechanism of toxicity, and the sensitivity of the analysis of a biomarker were identified as the key parameters to support such a decision. The procedure proposed for decision making is illustrated by case studies based on two documented chemical incidents in the Netherlands.