Despite routinely restoring epicardial coronary patency, with primary percutaneous coronary intervention (PCI), microvascular obstruction affects approximately half of patients and confers an adverse prognosis. There are no evidence-based treatments for microvascular obstruction. A key contributor to microvascular obstruction is distal embolisation and microvascular thrombi. Adjunctive intracoronary fibrinolytic therapy may reduce thrombotic burden, potentially reducing distal embolisation of atherothrombotic debris to the microcirculation. In this review, the evidence from published randomised trials on the effects of adjunctive intracoronary fibrinolytic therapy during primary PCI is critically appraised, the ongoing randomised trials are described, and conclusions are made from the available evidence. Clinical uncertainties, to be addressed by future research, are highlighted.