One of the factors that increase the effectiveness of the pharmacotherapy used in patients abusing various types of new psychoactive substances (NPSs) is the proper functioning of the liver. However, the articles published to date on NPS hepatotoxicity only address non-specific hepatic parameters. The aim of this manuscript was to review three advanced markers of hepatotoxicity in psychiatry, namely, osteopontin (OPN), high-mobility group box 1 protein (HMGB1) and glutathione dehydrogenase (GDH, GLDH), and, on this basis, to identify recommendations that should be included in future studies in patients abusing NPSs. This will make it possible to determine whether NPSs do indeed have a hepatotoxic effect or whether other factors, such as additional substances taken or hepatitis C virus (HCV) infection, are responsible. NPS abusers are at particular risk of HCV infection, and for this reason, it is all the more important to determine what factors actually show a hepatotoxic effect in them.