Several experimental therapeutics have been demonstrated to be safe and effective in animal models of neurological disorders, but have failed when they reached the clinic. Postulated factors that affected the poor clinical outcomes include the lack of proper treatment controls and clinically relevant animal models. This failure of lab-to-clinic translation has plagued many neuroprotective drugs for stroke. With this in mind, the stem cell therapy field has cautiously approached translating stem cell products for clinical application, in that a negative clinical trial may hinder the entire regenerative medicine therapeutics. Here, we discuss the many translational challenges associated with stem cell therapy in the setting of stroke.