Clinical-toxicological investigations are very helpful for the detection and assessment of the severity of questionable narcotics intoxications. In some cases, an initial case of clinical poisoning then progresses in the further course to a case of forensic relevance (for example after deliberate poisoning e.g, with knock-out drugs or with intend to commit murder, or in cases of intoxication in connection with a criminal offense).The specifics and problems of the analytical detection of these substances in clinical and forensic cases are explained with regard to the presented narcotic drugs. The information used comes from data from our own examination material and data from the literature.The spectrum of addictive substances has changed significantly in recent years. While established methods of detection are available for alcohol and classic drugs of abuse, new drugs with potential for abuse (such as methylphenidate, pregabalin) or NPS, GHB, GBL, and 4‑BD cannot be detected by conventional methods of immunochemistry in combination with chromatographic methods such as GC-MS and HPLC-DAD.An improvement in the measurement equipment for specialised laboratories performing such investigations is therefore required in order to be able to adequately care for patients and to clarify criminal offenses. In the interests of legal certainty, it is important for offenders, in the case of a foreign substance being supplied to a victim, to assume that it can also be proven. In addition, with regard to the reliability of officially stated prevalence data for narcotic drugs in drug-related deaths, greater safety should be sought in the collection of all relevant substances.