High-resolution mass spectrometry (HRMS) is now the method of choice in several toxicology contexts. This paper reviews HRMS approaches for research and application in various toxicology fields, focusing on drugs of abuse in clinical and forensic toxicology. Papers concerning HRMS applications in screening, quantification and metabolism of drugs of abuse in biological and non-biological samples were included. Specific applications for new psychoactive substances in contexts such as online libraries, bioinformatic tools (molecular networking) and methods combinations were also included. (C) 2021 Societe Francaise de Toxicologie Analytique. Published by Elsevier Masson SAS. All rights reserved.