The treatment of ischemic stroke is one of the great challenges in modern neurology. The localization and the size of the infarct determine the long-term disability of stroke survivors. Recent observations have revealed that stroke also alters the function of the immune system and vice versa: At the site of the infarct, a local inflammatory response develops that enhances brain lesion development. In experimental stroke, proof-of-concept studies confirm that inhibition of this immune response reduces lesion volume and improves outcome. In the peripheral blood of stroke patients, though, lymphocytopenia and monocyte dysfunction develop. These changes reflect a clinically relevant impairment of bacterial defense mechanisms because they are associated with an enhanced risk to acquire post-stroke infections. Stress hormones have been identified as important mediators of stroke-induced immune suppression. The pharmacological inhibition of beta adrenergic receptors, but not the inhibition of steroids, is effective in reducing infection and improving clinical outcome in experimental stroke; catecholamine release therefore appears causally related to stroke-induced immune suppression. Strong evidence supports the hypothesis that these immune alterations impact the clinical course of stroke patients. Thus, the development of new therapeutic strategies targeted to alter the immunological consequences of stroke appears promising. However, to date, the beneficial effects seen in experimental stroke have not been successfully translated into a clinical trial. This brief review summarizes the current understanding of the immunological consequences of ischemic stroke. Finally, we propose a concept that links the peripheral immune suppression with the development of local inflammation.