The Epstein-Barr virus (EBV) is an oncogenic Herpes virus involved in the induction of a variety of human tumours. It was the first virus found to encode microRNAs (miRNAs). MiRNAs are short, non-coding RNAs that in most cases negatively regulate gene expression at the post-transcriptional level. EBV-transformed cells express at least 44 mature viral miRNAs that target viral and cellular genes. In addition, EBV-infection severely deregulates the miRNA profile of the host cell. The presently available information indicates that the virus uses its miRNAs to inhibit the apoptotic response of the infected cell as a means to establish a latent infection. Likewise, EBV-encoded miRNAs interfere in the expression of viral genes in order to mask the infected cell from the immune response. Cellular targets of viral miRNAs are involved in protein traffic within the cell and regulate innate immunity. MiRNA profiling of diffuse large B-cell lymphoma (DLBCL) and nasal NK/T-cell lymphoma (NKTL) showed that only 2% of the miRNAs are derived from the virus, while viral miRNAs comprise up to 20% of the total miRNA in nasopharyngeal carcinoma (NPC) and probably contribute to the formation or maintenance of NPC. The presence of viral miRNAs in exosomes raises the fascinating possibility that virus-infected cells regulate gene expression in the surrounding tissue to avert destruction by the immune system. This article is part of a Special Issue entitled: MicroRNAs in viral gene regulation.