This report describes the cases of 2 young adult men with depressive symptoms who experienced severe and disruptive motor disturbances while taking serotonin reuptake inhibitors. Both patients had a long history of medication failures and complex presentations. Genetic testing was utilized to guide effective treatment plans and to provide insight into previous medication failures. Most notably, testing in these patients revealed variations in the serotonin transporter protein and cytochrome P450 2D6 and 2C19 enzymes. These cases demonstrate the utility of genetic testing in clinical practice to help identify effective treatment plans in psychiatric patients.