Certain postmortem case constellations require intensive investigation of the pattern of drug use over a long period before death. Hair analysis of illicit drugs has been investigated intensively over past decades, but there is a lack of comprehensive data on hair concentrations for antidepressants, antipsychotics, and benzodiazepines. This study aimed to obtain data for these substances. A LC-MS/MS method was developed and validated for detection of 52 antidepressants, antipsychotics, benzodiazepines, and metabolites in hair. Hair samples from 442 postmortem cases at the Institute of Legal Medicine of the Charité-University Medicine Berlin were analyzed. Postmortem hair concentrations of 49 analytes were obtained in 420 of the cases. Hair sample segmentation was possible in 258 cases, and the segments were compared to see if the concentrations decreased or increased. Descriptive statistical data are presented for the segmented and non-segmented cases combined (n = 420) and only the segmented cases (n = 258). An overview of published data for the target substances in hair is given. Metabolite/parent drug ratios were investigated for 10 metabolite/parent drug pairs. Cases were identified that had positive findings in hair, blood, urine, and organ tissue. The comprehensive data on postmortem hair concentrations for antidepressants, antipsychotics, and benzodiazepines may help other investigators in their casework. Postmortem hair analysis results provide valuable information on the drug intake history before death. Pattern changes can indicate if drug intake stopped or increased before death. Results should be interpreted carefully and preferably include segmental analysis and metabolite/parent drug ratios to exclude possible contamination.