The use of animal models remains critical in preclinical and translational research. The reliability of the animal models and aspects of their validity is likely key to effective translation of findings to medicine. However, despite considerable uniformity in animal models brought about by control of genetics, there remain a number of social as well as innate and acquired behavioral characteristics of laboratory animals that may impact on research outcomes. These include the effects of strain and genetics, age and development, sex, personality and affective states, and social factors largely brought about by housing and husbandry. In addition, aspects of the testing environment may also influence research findings. A number of considerations resulting from the animals' innate and acquired behavioral characteristics as well as their social structures are described. Suggestions for minimizing the impact of these factors on research are provided.