Oral fluid (OF) has become a valuable biologic specimen for toxicological analysis, especially in driving under the influence of drugs (DUID) investigations, because of easy and non-invasive collection procedures. In OF testing, being the sample volume is limited, multi-analyte procedures are particularly advantageous since they save time and resources. In this work, a procedure for the simultaneous analysis of 20 illicit drugs, belonging to the classes of cocaine, amphetamines, natural and synthetic opioids and hallucinogens, is presented. The sample preparation is based on microextraction by packed sorbent (MEPS), a novel technique which is based on the miniaturization of solid-phase extraction (SPE). The presented method, which includes all the most diffused illicit drugs and their metabolites, has been fully validated according to the Scientific Working Group for Forensic Toxicology (SWGTOX) guidelines. LLOQs ranged from 0.5 to 30 ng mL(-1) (diacetylmorphine); the presented method allows the detection of all the selected drugs quite below the cutoff values recommended by Substance Abuse and Mental Health Services Administration (SAMHSA) for abuse identification.