Animal models are often used to predict the effectiveness of treatments in humans, but their reliability in this regard remains controversial. Many interventions that show promise in animal studies fail in clinical trials, highlighting the challenges in translating findings from animals to humans. This review discusses the reasons behind these failures, including methodological flaws in animal studies, differences between animal models and clinical trials, and publication bias. It also emphasizes the importance of rigorous study design, including randomization, blinding, and proper sample size calculations, to improve the reliability of animal studies. The review highlights that publication bias can significantly overstate the efficacy of interventions in animal studies, leading to misleading conclusions. Additionally, the external validity of animal models is often compromised due to differences in disease pathophysiology, comorbidities, and treatment timing between animals and humans. The review calls for improved standards in the reporting of animal studies to ensure that clinical trials are based on high-quality, unbiased data. It also suggests that systematic reviews and meta-analyses of animal studies can help identify the most promising treatments for clinical trials. Overall, the review underscores the need for better alignment between animal research and clinical practice to improve the translation of findings from animal models to human patients.Animal models are often used to predict the effectiveness of treatments in humans, but their reliability in this regard remains controversial. Many interventions that show promise in animal studies fail in clinical trials, highlighting the challenges in translating findings from animals to humans. This review discusses the reasons behind these failures, including methodological flaws in animal studies, differences between animal models and clinical trials, and publication bias. It also emphasizes the importance of rigorous study design, including randomization, blinding, and proper sample size calculations, to improve the reliability of animal studies. The review highlights that publication bias can significantly overstate the efficacy of interventions in animal studies, leading to misleading conclusions. Additionally, the external validity of animal models is often compromised due to differences in disease pathophysiology, comorbidities, and treatment timing between animals and humans. The review calls for improved standards in the reporting of animal studies to ensure that clinical trials are based on high-quality, unbiased data. It also suggests that systematic reviews and meta-analyses of animal studies can help identify the most promising treatments for clinical trials. Overall, the review underscores the need for better alignment between animal research and clinical practice to improve the translation of findings from animal models to human patients.