Ischemic stroke is a crippling disease with few treatment options available. Thus there is an urgent need for novel therapies that can prevent or reverse the damaging effects of stroke. A promising experimental approach is stem cell therapy. Stem cells derived from human tissue, including embryonic, induced pluripotent, neural, and mesenchymal cells, are capable of rescuing injured brain tissue and improving functional recovery in experimental models of stroke. However, ethical issues, concerns regarding tumorigenicity, and diffi culty harvesting suffi cient cells may hamper their suitability as a widely available cell therapy for stroke patients. In contrast, placental- derived stem cells, particularly human amnion epithelial cells (hAECs), are abundant, non- immunogenic, non-tumorigenic and pose no ethical challenges. Surprisingly, hAECs have received little attention as a potential stroke therapy. This chapter will firstly describe the immune cell response and brain infl ammation after stroke, and then consider the potential for hAECs to improve stroke outcome given their unique properties. Protective actions of hAECs could involve modulation of the immune response, differentiation into neural tissue, re-innervation of lost connections, and secretion of important cytokines, growth factors, hormones and/or neurotransmitters to restore cellular function.