This chapter on the role of animal studies in preclinical therapeutic evaluation has been set within the context of acute ischemic, hemorrhagic and traumatic injuries. Although there has been a long list of translational failures in regards to neuroprotective drugs for ischemic stroke and TBI, this experience has provided us with several valuable lessons in regards to what we did wrong in past efforts and what we need to do better to achieve translational success in the future. Among these lessons is the knowledge that preclinical evaluation of drugs, gene therapies and cellular transplantation in animal models needs to be thorough and define the optimal treatment parameters, that is, dose, timing, duration, gender differences in responsiveness and how other pharmacological treatments may positively or negatively impact neuroprotective or neurorestorative efficacy. Subsequent to a thorough preclinical evaluation, clinical trial design needs to carefully consider and take full advantage of the therapeutic parameters derived from animal studies. Although preclinical evaluation in animal models needs to be thorough and statistically rigorous, careful consideration of animal welfare and minimization of sample sizes should not be ignored in the process.