Pulmonary embolism (PE) represents the third leading cause of cardiovascular death, despite the implementation of European Society of Cardiology guidelines, the establishment of PE response teams and advances in diagnosis and treatment modalities. Unfavorable prognosis may be attributed to the increasing incidence of the disease and pitfalls in risk stratification using the established risk stratification tools that fail to recognize patients with intermediate-high risk PE at normotensive shock in order to prevent further deterioration. In this light, research has been focused to identify novel risk stratification tools, based on the hemodynamic impact of PE on right ventricular function. Furthermore, a growing body of evidence has demonstrated that novel interventional treatments for PE, including catheter directed thrombolysis, mechanical thrombectomy and computer-assisted aspiration, are promising solutions in terms of efficacy and safety, when targeted at specific populations of the intermediate-high- and high-risk spectrum. Various therapeutic protocols have been suggested worldwide, regarding the indications and proper timing for interventional strategies. A ST-elevation myocardial infarction-like timing approach has been suggested in high-risk PE with contraindications for fibrinolysis, while optimal timing of the procedure in intermediate-high risk patients is still a matter of debate; however, early interventions, within 24-48 hours of presentation, are associated with more favorable outcomes.