AbstractChanges in the post‐mortem concentration of drugs, such as through redistributive processes are well known, although not well understood in terms of the mechanisms operating in particular cases and the extent it influences an interpretation of the reported concentrations. This advanced review outlines the mechanisms known to potentially alter blood and tissue concentrations and focuses on publications over the last decade that attempt to quantify the extent of changes occurring for specific drugs or drug classes. Most of the more recent studies show time‐dependent changes that do not always alter concentrations in one direction, let alone to the same extent. This increases the uncertainty of interpretation, particularly for drugs with a narrow therapeutic index. Nevertheless, guidelines are provided in this review to improve interpretation of post‐mortem drug concentrations in cases where a psychoactive substance(s) are a possible contribution to death.This article is categorized under: Toxicology > Post‐Mortem