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Stroke is a leading cause of death and disability worldwide, with ischemic stroke caused by an occluded vessel accounting for the majority of cases. Current treatments are limited to recanalization, either through thrombectomy or thrombolysis. Approved pharmacological interventions to suppress stroke‐associated excitotoxicity and neuroinflammatory events, leading to brain tissue death, are still lacking. Although numerous preclinical studies have been performed, they have yet to be translated into clinically relevant interventions. First‐line preclinical in vivo studies include the use of rodent ischemic stroke models, which vary in terms of how well they replicate human stroke pathophysiology and phenotype (including the formation of blood clot, blood–brain barrier disruption, neuroinflammation, and edema generation). Thus, rodent ischemic stroke models must be carefully chosen according to the specific pharmacological intervention to be tested. In this review, we aimed to provide an overview of the five most commonly used rodent ischemic stroke models and critically assess their advantages and limitations, with a primary focus on the acute phases of stroke. Ischemic stroke is a leading cause of death and disability, with current treatments limited to recanalization techniques and no approved pharmacological interventions for excitotoxicity and neuroinflammation. This review critically examines the five most commonly used rodent ischemic stroke models, evaluating their ability to replicate human stroke pathophysiology and phenotype, particularly in the acute phases. Rodent ischemic stroke models simulate key aspects of human ischemic stroke pathophysiology, but they do so to different degrees. Therefore, the choice of an appropriate model depends on the specific research goal at hand.Translational success in clinical trials has been limited, underscoring the need for improved model fidelity, standardized methodologies, and rigorous behavioral assessments.This review will guide researchers in the field towards the best‐suited model for a specific research question to improve the predictive value of their preclinical studies, and ultimately increase the likelihood of positive clinical outcomes.Future research should consider the impact of comorbidities on stroke outcomes to better mimic human stroke variability and pathophysiology in rodent ischemic stroke models. Rodent ischemic stroke models simulate key aspects of human ischemic stroke pathophysiology, but they do so to different degrees. Therefore, the choice of an appropriate model depends on the specific research goal at hand. Translational success in clinical trials has been limited, underscoring the need for improved model fidelity, standardized methodologies, and rigorous behavioral assessments. This review will guide researchers in the field towards the best‐suited model for a specific research question to improve the predictive value of their preclinical studies, and ultimately increase the likelihood of positive clinical outcomes. Future research should consider the impact of comorbidities on stroke outcomes to better mimic human stroke variability and pathophysiology in rodent ischemic stroke models.