Hepatitis E virus (HEV) superinfection has a significant impact on a natural course of chronic hepatitis B (CHB) patients with underlying chronic liver disease (CLD). These patients usually present with increased symptoms, rapid decompensation to liver failure, and increased mortality. An increasing rate of HEV infections worldwide with uncertainties in its prevention and treatment raises a great concern to this group of patients. Therefore, in this article, we reviewed recent studies describing the epidemiological patterns of HEV and Hepatitis B virus (HBV), both mono and dual infections. We also reviewed the literature on clinical interaction among HBV/HEV-superinfected patients with CLD and the potential preventive strategies.