Management of patients with acute pulmonary embolism may be very complex, and initial strategies will sometimes need to be changed. Very little data and no guidelines exist regarding decision-making and outcomes when strategies have to be changed. In this chapter, we detail five complex cases five complex cases managed by the Pulmonary Embolism Response Team of the University Hospital of Wales in Cardiff, UK, whereby some difficult choices had to be made, some of which worked out, but some of which required adaptability, are discussed in detail. We discuss the importance of teamwork, humility, and adaptability when dealing with pulmonary embolism, which frequently presents challenges in a way that few other diseases do. We attempt to extract lessons learned from cases where there may have been no single “right way” to manage each patient.