Epstein-Barr virus (EBV) is a human herpesvirus that persistently infects its host for a lifetime through a strategy of growth transforming resting B-cells into continuously proliferating lymphoblastoid cell lines (LCLs) while maintaining itself as an incomplete or “latent” virus in the infected cell nucleus. Immune surveillance is critical to maintaining this symbiosis as perturbations to T-cell immunity reveal the malignant potential of latent EBV-transformed B-cells. Epidemiological evidence further associates EBV infection with the development of other malignancies including Hodgkin’s lymphoma, Burkitt’s lymphoma, and nasopharyngeal carcinoma. Genetic and biochemical analyses have revealed that five viral proteins are essential for transformation by commandeering signal transduction pathways or intervening in transcriptional control. Latent infection membrane protein 1 (LMP1), a principal effector of transformation signaling, is a constitutively active receptor that exploits the tumor necrosis factor receptor-signaling pathway. This chapter reviews current models regarding the molecular mechanisms through which LMP1 enables EBV to transform B-cell growth.