This case comparison illustrates pharmacogenetic testing in psychotropic and clinical management in relation to the ABCB1 gene, which encodes the P-glycoprotein transporter affecting blood-brain barrier (BBB) permeability. Two pediatric patients (9 and 11 years old) were selected for similar clinical presentations with opposing ABCB1 genotype, while they were identically matched for key CYP450, dopaminergic and serotonergic genes (CYP2C9, CYP2C19, DRD2, SLC6A4, 5HTR2A). Case A was functional for the ABCB1 gene (G/G rs1045642), suggesting that the BBB had a functional P-glycoprotein transporter. Case B was subfunctional for the ABCB1 gene (A/A rs1045642), suggesting that the patient's BBB may be permeable to psychotropic drugs. Case A had more medication trials and dose adjustments than Case B. Case A had two inpatient admissions and interspersed emergency room visits, while case B had none.