Hyperglycemia is frequently found (40–60%) after all kinds of stroke and it has been related to increased lesion size and poor clinical outcome. In this chapter, we will primarily focus on ischemic stroke; we will outline the incidence and natural course of post-stroke hyperglycemia and discuss the possible etiologies of post-stroke hyperglycemia. Subsequently, we will present an overview of various mechanisms that could explain how hyperglycemia is detrimental after ischemic stroke. Finally, we will address the question whether in-hospital hyperglycemia should be treated in stroke patients, and if so decided, the glucose levels that should be targeted and the difficulties that arise in achieving this.