Geographical and ethnic diversity in Nepal has led to interesting epidemiology of viral hepatitis and liver diseases. Before the epidemic of Biratnagar that occurred in April to June 2014, Kathmandu was the only known endemic region for hepatitis E virus infection (HEV), where at least four previous epidemics have been documented since 1973. Due to rapid urbanization with still low socioeconomic condition, other major cities are appreciated to be at increasing risk of outbreaks. Characteristics of HEV epidemics and genetic changes of HEV during last decade have been studied. While hepatitis A virus infection was only common during childhood till recent years, it is re-emerging as an important etiology of acute hepatitis in young adults. Nepal is classified as low endemic region for hepatitis B virus infection (HBV) with overall seroprevalence of 1.1%. But, some ethnic groups and geographical areas have high prevalence rates. Despite low endemicity, HBV accounts for majority of cases of hepatocellular carcinoma and liver cirrhosis in the country. Similarly, though hepatitis C virus (HCV) is present in only 0.4% of general population, high seroprevalence was found among intravenous drug abusers many of them with HIV coinfection. Apart from hepatitis viruses, alcohol use also contributes significantly to liver cirrhosis and chronic liver failure. A unique form of hepatic venous outflow obstruction called ‘hepatic vena cava syndrome’ has been identified as an important etiology of liver cirrhosis and hepatocellular carcinoma.