The authors use a previously published decision-making algorithm to address the role of clinical pharmacokinetic monitoring of ganciclovir, the drug of choice for prophylaxis and treatment of cytomegalovirus (CMV) in solid organ transplant recipients. Ganciclovir pharmacokinetics have been studied in solid organ transplant recipients with a wide range of peak and trough concentrations reported. Numerous assays are available to measure plasma concentrations of ganciclovir, but no clear correlation has been established between peak or trough concentrations and either efficacy or toxicity of the drug. For patients receiving treatment, the pharmacological response of ganciclovir is assessed initially by clinical response. Monitoring prophylactic therapy in asymptomatic patients poses a greater challenge. Although monitoring of antigenemia or polymerase chain reaction (PCR) deoxyribonucleic acid (DNA) is not yet part of routine clinical practice, studies have shown a role for these techniques in monitoring response to antiviral therapy. Studies of subpopulations of renal failure patients show a prolonged ganciclovir half-life that requires dosage adjustments. However, ganciclovir clearance is closely correlated with creatinine clearance, which is an appropriate approach to adjusting dosages. Studies in pediatric patients also demonstrate a close correlation between dose per kilogram and AUC, suggesting that monitoring of ganciclovir levels may not be necessary. Based on the evidence presented in this review, routine clinical pharmacokinetic monitoring of ganciclovir does not appear to be warranted in solid organ transplant recipients.