MicroRNAs (miRNAs) are a class of small ∼22 nt regulatory RNAs that modulate mRNA expression in all multicellular eukaryotic organisms. Interestingly, viruses also encode miRNAs and these viral miRNAs target cellular and viral mRNAs to regulate virus replication and latent infection. In particular, herpesviruses encode a large number of miRNAs. Herpesvirus infection also changes the normal expression profile of cellular miRNAs. New genetic tools have recently been generated to study the function of viral and cellular miRNAs in virus-infected cells. The creation of these reagents and use in Epstein-Barr virus-infected lymphoblastoid cell lines are discussed as a model viral system for the investigation of miRNA function.