Stroke remains a major cause of serious disability due to the brain’s limited capacity to regenerate. Current treatments focus on acute recanalization of the occluded blood vessels; however, currently there are no approved therapy options to regenerate neural circuits and reduce stroke-related disability. To promote recovery, therapeutic angiogenesis has been proposed as a promising target. Although restoration of blood vessels providing oxygen and nutrients to the peri-infarct regions may be beneficial, newly generated capillaries may also carry pathophysiological risk factors that need to be considered. One major concern are adverse effects including edema formation and haemorrhagic transformation due to the comprised endothelial barrier function during vascular remodelling. This brief opinion article will discuss the challenges and the newest advancements of angiogenesis as a therapeutic strategy for ischemic stroke.