Toxicity testing relies heavily on animals, especially rodents as part of the non-clinical laboratory testing of substances. However, the use of mammalians and the number of animals employed in research has become a concern for institutional ethics committees. Toxicity testing involving rodents and other mammals is laborious and costly. Alternatively, non-rodent models are used as replacement, as they have less ethical considerations and are cost-effective. Of the many alternative models that can be used as replacement models, which ones can be used in predictive toxicology? What is the correlation between these models and rodents? Are there standardized protocols governing the toxicity testing of these commonly used predictive models? This review outlines the common alternative animal models for predictive toxicology to address the importance of these models, the challenges, and their standard testing protocols.