This review summarizes the literature to date relating to pyrolysis and heated vapour ingestion of drugs of abuse. In this context, heating is referred to as smoking or pyrolysis, but these are generic descriptors that encompass numerous methods of vapour generation and inhalation. Depending on the amount of drug used, diluents and contaminants present, heating conditions, and the oxidative/reductive environment, many thermal decomposition products can be formed. In addition to the recognized hazard of rapid onset of pharmacological effects of the parent drug, thermal decomposition products may be pharmacologically active as well as acutely/chronically toxic. For example, several published reports have linked heroin smoking to a form of brain encephalopathy and to the development of movement disorders. Early qualitative studies focusing on the thermal decomposition of drugs have evolved into more complex investigations employing mass spectral identification, confirmation, and elucidation of formation mechanism. In most cases, thermal decomposition begins with cleavage of the weakest bond (often C-N) to generate free radicals that then form the most stable sterically favoured products. Several reports of rearrangements at higher temperatures have been identified and hint at an underlying complexity that arises from the variety of smoking methods and conditions. Given that many designer drugs such as synthetic cannabinoids are ingested primarily through smoking, this issue has taken on new importance.