The immune system is intricately involved in brain development and physiological neuronal function. The influence of the adaptive immune system on several brain diseases has been described in great detail. In ischemic stroke, numerous studies have particularly demonstrated a key role for T cells during the acute phase after the brain injury. Recently, a critical role for T cells has also become more evident for the chronic phase after stroke in modulating delayed neuronal (dys-) function and recovery. Here, T cells may also affect various non-immunological pathways by interacting with brain-resident immune cells and modulating mechanisms such as neurogenesis and angiogenesis. This novel concept suggests T cells as potential therapeutic targets to modulate post-stroke regeneration.