Cytokines are mediators of cellular communication produced by multiple liver cell types. Cytokines can directly induce either necrosis or apoptosis. They can also recruit such cells as neutrophils and lymphocytes, which can mediate liver damage. Increased levels of hepatotoxic cytokines such as tumor necrosis factor-alpha are documented in alcoholic liver disease (ALD) and nonalcoholic steatohepatitis (NASH) and have been shown to play a mechanistic role in both of these disease processes. Transforming growth factor-beta is a profibrotic cytokine that is critical in hepatic fibrosis. Beneficial cytokines, such as interleukin (IL)-10 and -6, also exist. Such beneficial cytokines as adiponectin are made outside the liver and appear to protect against ALD and NASH. This article reviews the relevance of cytokines in human and experimental forms of liver injury, focusing on modulation of cytokines and the use of beneficial cytokines in treatment and prevention of liver injury in ALD, NASH, and hepatitis C.