Sexual assault is defined as any undesired physical contact of a sexual nature perpetrated against another person and is a prevalent problem presenting at emergency departments, emergency forensic medicine units, and rape crisis centres worldwide. Drug-facilitated sexual assault (DFSA) is a complex problem that is encountered with increasing frequency. But this problem is often underrepresented because most DFSAs are not reported by the frightened victims or are diagnosed as an acute drug or alcohol intoxication, thereby bypassing sexual abuse diagnosis and appropriate care. Proper care must be taken to ensure the chain of custody. Emergency physicians need to be aware of the phenomenon and work together with reference emergency forensic medicine units and rape crisis centres, which are capable of taking care of the male and female victims of sexual abuse. If no attention is given to the risk of DFSA, then toxicological samples (urine, blood, hair) and other biologic evidence may remain unidentified and semen, vaginal secretions, and vaginal epithelial cells cannot be genetically typed by a crime laboratory. This article reports the main clinical aspects of DFSA encountered in emergency departments at the beginning of the 21st century and the experience of an emergency forensic medicine unit based at a hospital (Compiègne, France). Guidelines are proposed for clinical examination of DFSA victims, clinical forensic medical examination, and accurate samplings for further toxicological and biological evidence.