Duloxetine (Cymbalta) is manufactured by Eli Lilly and Company and is the newest antidepressant to be approved by the Food and Drug Administration (FDA). Duloxetine is a potent serotonin and norepinephrine reuptake inhibitor that is also used for the management of pain associated with diabetic peripheral neuropathy. With the introduction of any new drug, toxicology laboratories around the nation experience the same problems: lack of information about the chemical and physical properties of the new drug, detection methodologies from biological specimens, and interpretation of quantitative values. Since its FDA approval in 2002, the Los Angeles County Department of Coroner Toxicology Laboratory has detected and quantitated duloxetine in 12 postmortem cases. The isolation of duloxetine from postmortem specimens consisted of a basic, liquid-liquid (n-butylchloride) extraction procedure. Duloxetine was detected in our general, pharmaceutical, basic drugs screen that utilizes gas chromatography-nitrogen-phosphorus detection (GC-NPD) and GC-mass spectrometry (MS), and the quantitation was specifically by GC-MS. Linearity was achieved from 0.05 to 3.0 mg/L with the limit of detection at 0.03 mg/L. Presented are the case histories, demographics, cause/manner of death, and the postmortem tissue distribution ranges of duloxetine: central blood, not detected (ND)-0.59 mg/L (12 cases); femoral blood, ND-0.26 mg/L (9 cases); vitreous humor, ND-0.23 mg/L (4 cases); liver, 0.28-22 mg/kg (8 cases); gastric contents, 0.08-86 mg total (6 cases); bile, 0.57-3.1 mg/L (7 cases); and urine, 0.07-0.47 mg/L (6 cases). The detection and quantitation of duloxetine in these 12 case studies are considered the first to be reported in the literature; all are designed to aid the forensic toxicologist with the interpretation of his/her own casework.