Pulmonary embolism (PE) is a serious and prevalent cause of vascular disease. Nevertheless, optimal treatment for many phenotypes of PE remains uncertain. Treating PE requires appropriate risk stratification as a first step. For the highest-risk PE, presenting as shock or arrest, emergent systemic thrombolysis or embolectomy is reasonable, while for low-risk PE, anticoagulation alone is often chosen. Normotensive patients with PE but with indicia of right heart dysfunction (by biomarkers or imaging) constitute an intermediate-risk group for whom there is controversy on therapeutic strategy. Some intermediate-risk patients with PE may require urgent stabilization, and ≈10% will decompensate hemodynamically and suffer high mortality, though identifying these specific patients remains challenging. Systemic thrombolysis is a consideration, but its risks of major and intracranial hemorrhages rival overall harms from intermediate PE. Multiple hybrid pharmacomechanical approaches have been devised to capture the benefits of thrombolysis while reducing its risks, but there is limited aggregate clinical experience with such novel interventional strategies. One method to counteract uncertainty and generate a consensus multidisciplinary prognostic and therapeutic plan is through a Pulmonary Embolism Response Team, which combines expertise from interventional cardiology, interventional radiology, cardiac surgery, cardiac imaging, and critical care. Such a team can help determine which intervention—catheter-directed fibrinolysis, ultrasound-assisted thrombolysis, percutaneous mechanical thrombus fragmentation, or percutaneous or surgical embolectomy—is best suited to a particular patient. This article reviews these various modalities and the background for each.