The Stroke Therapy Academic Industry Roundtable (STAIR) has updated its preclinical recommendations to improve the quality and reproducibility of studies evaluating acute stroke therapies. The updated guidelines emphasize the importance of defining dose response and therapeutic windows using both histological and functional outcomes in multiple animal species with appropriate physiological monitoring. Key recommendations include eliminating randomization and assessment bias, defining inclusion/exclusion criteria a priori, performing power and sample size calculations, and disclosing potential conflicts of interest. Studies should be conducted in females, aged animals, and animals with comorbid conditions such as hypertension, diabetes, and hypercholesterolemia. The use of clinically relevant biomarkers in animal studies is also recommended. While these guidelines cannot be validated until effective therapies emerge from clinical trials, adherence to them may enhance the chances of success. The article discusses the limitations of current animal models and the need for better linkage between animal models and clinical stroke. It also highlights the importance of fostering cooperation among stakeholders, including academia, regulatory agencies, and pharmaceutical companies, to overcome the challenges in drug development.The Stroke Therapy Academic Industry Roundtable (STAIR) has updated its preclinical recommendations to improve the quality and reproducibility of studies evaluating acute stroke therapies. The updated guidelines emphasize the importance of defining dose response and therapeutic windows using both histological and functional outcomes in multiple animal species with appropriate physiological monitoring. Key recommendations include eliminating randomization and assessment bias, defining inclusion/exclusion criteria a priori, performing power and sample size calculations, and disclosing potential conflicts of interest. Studies should be conducted in females, aged animals, and animals with comorbid conditions such as hypertension, diabetes, and hypercholesterolemia. The use of clinically relevant biomarkers in animal studies is also recommended. While these guidelines cannot be validated until effective therapies emerge from clinical trials, adherence to them may enhance the chances of success. The article discusses the limitations of current animal models and the need for better linkage between animal models and clinical stroke. It also highlights the importance of fostering cooperation among stakeholders, including academia, regulatory agencies, and pharmaceutical companies, to overcome the challenges in drug development.