Patients presenting with pulmonary embolism (PE) have a wide spectrum of clinical severity. Although some patients may present with frank hemodynamic collapse and cardiac arrest, others may present with an asymptomatic PE that is discovered incidentally during workup of another condition. Fibrinolytic therapy is an option in the treatment of patients with PE due to its ability to rapidly dissolve thromboemboli clots. However, the use of fibrinolytics in the treatment of PE is a controversial topic that has left many practicing physicians confused on how to best treat these patients. A rational approach to deciding whether fibrinolytic therapy is indicated is based on an assessment of the benefit that each particular patient will derive from fibrinolytic therapy weighed against that patients risk for major bleeding and intracranial hemorrhage. There is a clear benefit/risk ratio for fibrinolytic therapy in patients with PE who present with cardiac arrest and in those who are hemodynamically unstable from a massive PE. With proper risk assessment, select patients with stable hemodynamics and right ventricular dysfunction may also benefit from fibrinolytic therapy. There is no benefit to fibrinolytic treatment in patients with stable hemodynamics and normal right ventricular function. This article sets out to review the literature on fibrinolytic therapy in the treatment of patients with PE and will propose an evidence based treatment algorithm.