Anticoagulation is the cornerstone of acute pulmonary embolism (PE) therapy. Intermediate-risk (submassive) or high-risk (massive) PE patients have higher mortality than low-risk patients. It is generally accepted that high-risk PE patients should be considered for more aggressive therapy. Intermediate-risk patients can be subdivided, although more than simply categorizing the patient is required to guide therapy. Therapeutic approaches depend on a prompt, detailed evaluation, and PE response teams may help with rapid assessment and initiation of therapy. More clinical trial data are needed to guide clinicians in the management of acute intermediate- and high-risk PE patients.