Management of pulmonary embolism in individuals with thrombocytopenia requires attentive consideration weighing the risks of thrombus propagation with known bleeding risks ascribed to anticoagulation therapy. The degree of thrombocytopenia imparts risk for bleeding and greatly impacts therapeutic strategies. Understanding the mechanism for thrombocytopenia, whether due to platelet destruction or limited production, is essential in formulating treatment approaches. Diagnostic examination for thrombocytopenia should include confirmation with a platelet count as well as evaluation of other cell lines (white blood cells and red blood cells), as this will help narrow differential causes. It is important to recognize certain conditions that carry a prothrombotic state with thrombocytopenia, such as malignancy, antiphospholipid syndrome, heparin-induced thrombocytopenia, thrombotic microangiopathies, and immune thrombocytopenia. Treatment of thrombosis in the setting of thrombocytopenia necessitates a careful balance to reduce the risk for clot recurrence or progression while circumventing complications such as major bleeding events. When selecting an appropriate therapeutic strategy for thrombosis in the situation of continued thrombocytopenia, for instance in malignancy or ITP, the degree of thrombocytopenia as well as identification of high-risk features, such as recent symptomatic pulmonary embolism or prior history of venous thromboembolism, can help determine the role of platelet transfusion support and anticoagulation dosing. The use for thrombolysis or thrombectomy in clinical setting of thrombocytopenia remains uncertain and management strategies should be determined on an individual case basis. Further data is required for management of thrombosis with concurrent thrombocytopenia. In particular, the efficacy and tolerability of direct oral anticoagulants, the function of thrombolytic strategies, and assessment of bleeding risk with anticoagulation at varying degrees of thrombocytopenia. With novel advancements in management for a number of causes for thrombocytopenia, these inventive treatments should be further evaluated in the setting of pulmonary embolism to help guide management strategies for thrombosis in the setting of thrombocytopenia.