The liver is a vital organ, which is responsible for digestion and detoxification. Traditional studies on hepatotoxicity of xenobiotics are relied on in vivo animal models for data collection, however, animal tests are time consuming and expensive, and sometimes fail to predict human toxicity. To follow “3R” principle (Replacement, Reduction, Refinement), more in vitro models have become more popular for the assessment of hepatotoxicity. This review presents a brief overview and comparison of some in vitro liver models, as well as prospects for future development.