The use of molecular tests for the diagnosis of viral infections in solid organ transplant recipients is increasing, in part because of the increased sensitivity and rapid turnaround time of these tests. A variety of molecular methods are now available for the detection and quantification of viral pathogens, including polymerase chain reaction, nucleic acid sequence based amplification, transcription mediated amplification, hybrid capture, and branched DNA. A key challenge facing clinicians when diagnosing herpesvirus infections with molecular assays is distinguishing latent from active infection. Methods to improve the clinical specificity of molecular assays have been developed and are reviewed. A major limitation to the widespread use of molecular assays for the diagnosis and monitoring of viral infections in solid organ transplant recipients is the lack of standardized assays. The availability of such assays will allow the establishment of interpretive guidelines that can be broadly applied in clinical practice.