Optimizing valganciclovir dosing strategies: a comprehensive review.2025 · INTRODUCTION: Orally administered valganciclovir (VGCV) is rapidly metabolized to ganciclovir (GCV) and is used to prevent and treat cytomegalovirus (CMV) infection. Although GCV exposure is related to efficacy or toxicity, therapeutic drug monitoring (TDM) for GCV has not yet been clinically implemented. This review was conducted to summarize relevant current issues for implementing the optimization of VGCV therapy based on TDM. AREAS COVERED: The current knowledge on the population pharmacokinetics of GCV after oral administration of VGCV, the relationships between GCV exposure with efficacy and toxicity, and the available evidence for TDM was comprehensively reviewed. The limited sampling strategy (LSS) and microsampling methods for clinically implementing TDM are summarized. The relationship between nucleoside-diphosphate-linked moiety X-type motif 15 (NUDT15) polymorphisms and toxicity is discussed. Relevant literature published before 2025 was searched in PubMed. EXPERT OPINION: Accumulating evidence indicates that GCV exposure is associated with both efficacy and safety, and exposure-guided dosing (target area under the time-concentration curve (AUC) of 40-60 μg·h/mL) may provide a reliable approach for maximizing VGCV therapy. However, several methodological and practical challenges, including standardization of LSS and improvement of microsampling technologies, are required for practical VGCV dose optimization in all patient populations.