In postmortem toxicology, the identity and quantity of drugs and poisons present in postmortem specimens is determined to assist in establishing the circumstances surrounding the death of individuals. Microbial activity may affect this quantitation by (i) limiting the amount and quality of biological specimens available for analysis, due to the decomposition of human remains; and (ii) altering drug, poison, and metabolite concentrations, due to their decomposition. While specimens obtained at autopsy may be stored at low temperatures and with preservatives to minimize degradation, conditions prior to body receipt at the mortuary are not controllable. Thus, microbial activity can complicate the interpretation of analytical results, particularly if the stability of the analyzed substances in a putrefactive environment is unknown. This chapter is primarily a review of past studies, where the significance of microbial activity on the changing concentrations of specific drugs, poisons, and metabolites has been assessed.