The article discusses the limitations of animal models in drug development and the need for more accurate and humane alternatives. Animal models, such as mice and rats, have long been used in medical research to understand disease and test potential treatments before human trials. However, overreliance on animal models can lead to misleading results and clinical trial failures. The article explains how animal research is used in drug development, its benefits and limitations, and how more accurate human-cell-based and computer models could improve this process. Historically, animal experiments were the predominant technology in life sciences, peaking in the 1970s for drug development. Other methods have now begun to complement and even replace animal testing, despite its continued high regard in scientific and regulatory circles. Ethical concerns were the primary drivers for questioning the use of animal experiments; the debate over the justification of animal suffering for scientific advancement varies, but public opinion is increasingly critical. In response, the scientific community has implemented measures to make animal experiments more rigorous, requiring formal justifications, permissions, and adherence to rising standards of animal welfare. Concurrently, there has been significant support for developing alternatives. Recent challenges to animal experiments extend beyond ethics. They are resource-intensive, costly, time-consuming, and have limited predictivity for humans—issues highlighted by the European REACH program’s struggle to test thousands of industrial chemicals and by the pharmaceutical industry’s crisis of low success to the market. The latter refers to the extremely high failure rate in clinical trials for drug candidates due to issues like lack of efficacy or safety problems in human testing. These problems have sparked a broader discussion on the “reproducibility crisis” in science. The drive to find alternatives to traditional animal testing—notably in toxicology, which uses about 10% of all experimental animals (according to European statistics)—has led to significant work in this area. Reasons why most work into alternatives takes place in toxicology include government funding, legislative acts like the European cosmetics test ban and REACH chemical legislation, and the relative stability of internationally standardized guideline tests. Despite all biomedical progress, we are far from understanding the complex networked systems of the human organism and, even farther, their perturbation in disease. Intervening in these disease mechanisms as a remedy involves much trial and error. Increasingly, identifying a certain mechanism of disease or a possible target for a drug can change the odds of finding something that ultimately works. Such so-called pharmacological "targets" can be, for example, a misbehaving cell type or a receptor protein on cells in an organ that positively influences the course of disease or ameliorates a certain symptom. These observations (on the cell types or receptors) may often occur in animal "models" of disease, and this species difference compounds the difficulty with translating observations from the laboratory bench to the clinic. It is still an enormous undertaking to develop a therapy from this and bring a successful drug to the market. On average, drugThe article discusses the limitations of animal models in drug development and the need for more accurate and humane alternatives. Animal models, such as mice and rats, have long been used in medical research to understand disease and test potential treatments before human trials. However, overreliance on animal models can lead to misleading results and clinical trial failures. The article explains how animal research is used in drug development, its benefits and limitations, and how more accurate human-cell-based and computer models could improve this process. Historically, animal experiments were the predominant technology in life sciences, peaking in the 1970s for drug development. Other methods have now begun to complement and even replace animal testing, despite its continued high regard in scientific and regulatory circles. Ethical concerns were the primary drivers for questioning the use of animal experiments; the debate over the justification of animal suffering for scientific advancement varies, but public opinion is increasingly critical. In response, the scientific community has implemented measures to make animal experiments more rigorous, requiring formal justifications, permissions, and adherence to rising standards of animal welfare. Concurrently, there has been significant support for developing alternatives. Recent challenges to animal experiments extend beyond ethics. They are resource-intensive, costly, time-consuming, and have limited predictivity for humans—issues highlighted by the European REACH program’s struggle to test thousands of industrial chemicals and by the pharmaceutical industry’s crisis of low success to the market. The latter refers to the extremely high failure rate in clinical trials for drug candidates due to issues like lack of efficacy or safety problems in human testing. These problems have sparked a broader discussion on the “reproducibility crisis” in science. The drive to find alternatives to traditional animal testing—notably in toxicology, which uses about 10% of all experimental animals (according to European statistics)—has led to significant work in this area. Reasons why most work into alternatives takes place in toxicology include government funding, legislative acts like the European cosmetics test ban and REACH chemical legislation, and the relative stability of internationally standardized guideline tests. Despite all biomedical progress, we are far from understanding the complex networked systems of the human organism and, even farther, their perturbation in disease. Intervening in these disease mechanisms as a remedy involves much trial and error. Increasingly, identifying a certain mechanism of disease or a possible target for a drug can change the odds of finding something that ultimately works. Such so-called pharmacological "targets" can be, for example, a misbehaving cell type or a receptor protein on cells in an organ that positively influences the course of disease or ameliorates a certain symptom. These observations (on the cell types or receptors) may often occur in animal "models" of disease, and this species difference compounds the difficulty with translating observations from the laboratory bench to the clinic. It is still an enormous undertaking to develop a therapy from this and bring a successful drug to the market. On average, drug