Epstein-Barr virus (EBV) is the first identified oncogenic virus. It causes three types of diseases: lymphomas, carcinomas, and autoimmune diseases. It is estimated that two hundred thousand deaths are due to EBV each year. After a primary infection, EBV can remain latent lifelong. Reactivation to lytic phase can be induced by various drugs including small organic molecules, biologics, or a combination of both. In this review, we identified the most relevant results obtained with small organic compounds against Epstein-Barr virus-associated diseases. Specific treatments targeting Epstein-Barr Nuclear Antigen 1 are emerging concerning small organic molecules and showed promising results against several EBV-related malignancies.