Human cytomegalovirus remains an important pathogen for transplant recipients. To date, a limited number of drugs have been licensed for the treatment of HCMV infection and disease, all sharing the same target molecule, the viral DNA-polymerase. Although combating HCMV with DNA-polymerase inhibitors is effective and has been established for many years, there are several drawbacks associated with the use of these drugs including toxicity and emergence of drug resistance. In order to overcome these problems different treatment options and durations have been assessed and new and improved antiviral drugs with novel molecular targets have been discovered. However, not all of these novel drugs had the properties for success in clinical development, and alternative treatment options with known drugs have been evaluated in parallel. Today the need for an antiviral drug that is potent, safe and well tolerated remains.