More aggressive therapy for acute pulmonary embolism beyond anticoagulation is indicated in patients at higher risk for mortality and morbidity, namely those suffering from massive and possibly submassive disease. Catheter-based thrombolysis, catheter-based mechanical thrombus debulking, or combinations of these offer opportunities for rapid clot reduction and clinical improvement with a lower bleeding risk than systemic thrombolysis and perhaps greater efficacy. Optimal low-dose regimens for direct thrombolysis have not been defined just as optimal techniques and devices for mechanical therapy have not been developed, underscoring the need for further work.