Abstract: Nonhuman animal (“animal”) experimentation is typically defended by arguments that it is reliable, that animals provide sufficiently good models of human biology and dis- eases to yield relevant information, and that, consequently, its use provides major human health benefits. I demonstrate that a growing body of scientific literature critically assessing the validity of animal experimentation generally (and animal modeling specifically) raises important concerns about its reliability and predictive value for human outcomes and for understanding human physiology. The unreliability of animal experimentation across a wide range of areas undermines scientific arguments in favor of the practice. Additionally, I show how animal experimentation often significantly harms humans through misleading safety studies, potential abandonment of effective therapeutics, and direction of resources away from more effective testing methods. The resulting evidence suggests that the collective harms and costs to humans from animal experimentation outweigh potential benefits and that resources would be better invested in developing human-based testing methods.