Tacrolimus is the cornerstone in pediatric liver transplant immunosuppression. Despite close monitoring, fluctuations in tacrolimus blood levels affect the safety and efficacy of immunosuppressive drugs. Among several factors, the impact of the cytochrome CYP3A5 genotype on tacrolimus concentrations after transplantation is important. We report herein a case of a pediatric recipient of a living-donor liver transplant. After transplantation, a 4.7-fold increase in tacrolimus dosage and a 4.2-fold increase in tacrolimus clearance were observed and associated with a 9-day delay to attain levels within the therapeutic range. Recipient and donor DNA was genotyped and both were observed to be carriers of the CYP3A5*1*1 genotype (CYP3A5 expressor). In this patient, the contribution of the CYP3A5 genotype is crucial and influenced tacrolimus disposition, the adjustment of the tacrolimus dose, and the time to reach the therapeutic range in the early stages after transplantation.