Abstract: The development of efficient ways to predict, prevent, diagnose and treat human diseases is of great interest to human society and is a focus of life science research. It is widely believed that all human diseases may be attributed to the interaction between genetic and environmental risk factors, and this interaction influences the genesis, course, drug response and outcome of the diseases. The most effective approach for research into human diseases is the clinical study, but this can be hampered by disease heterogeneity, marked individual differences and the difficulty in tracking the history and course of a disease. Additionally, no study should be performed on humans without preclinical assessments in non-human animals. The best strategy for research into human diseases is to use animal models that mimic the genesis, course, drug response and outcomes of human disease and where the etiology, genetic background and environmental factors can be strictly controlled, unfeasible in clinical studies of humans. However, there are many problems associated with the study of animal models for human disease, some of which are based on misunderstanding. For this special issue of Zoological Research we discuss these problems and misunderstandings.