In 2001 valganciclovir was approved by the FDA for treatment of HIV associated retinitis and in 2003 for prevention of post transplant CMV. This review provides an update on the status of its use and areas of controversy: How long should prophylaxis be given?; What is the appropriate dose for prophylaxis?; Can it be used in children, and at what dose?; Can it be used to treat CMV disease? The question of optimal dosing will probably not be settled as the sample size for controlled trials would be prohibitive. Other trials clearly show that extended therapy provides added benefit, the drug is safe and an appropriate dose has been identified in children and oral therapy of CMV disease is effective.