Since early reperfusion therapy for patients with acute myocardial infarction (AMI) was demonstrated to decrease mortality, numerous improvements in AMI management have focused on prompt reperfusion of the epicardial coronary arteries. However, in a substantial group of patients with AMI, reperfusion of the myocardial tissue is hindered by dysfunction of the microvasculature, despite successful restoration of the epicardial coronary flow. These patients have prolonged ischemia and an adverse clinical outcome. Although several studies investigating the etiology of microvascular dysfunction have been performed, little is known about the restoration process of microvascular dysfunction after reperfused AMI. The objective of this Review is to summarize our knowledge on natural restoration of the microvasculature after reperfused AMI, particularly with regard to angiogenesis, discuss diagnostic modalities used to identify patients with microvascular dysfunction and highlight the potential of pharmacological and cellular interventions to stimulate the recovery of the microvasculature by promoting angiogenesis.