Heparin-induced thrombocytopenia (HIT) is an autoantibody-mediated response to heparin exposure resulting in activated platelets, subsequent thrombocytopenia, and life-threatening thrombotic events. HIT has a greater incidence in surgical compared to medical patients and occurs in approximately 1:1500–5000 hospitalized patients. Thrombocytopenia is present in more than 90% of cases and occurs within 5–10 days following heparin exposure, and approximately one-half of patients experience a thrombotic event. Diagnosis starts with calculating the 4Ts score followed by detecting the presence of PF4-heparin antibodies and confirming with functional assays. The cornerstone of treatment is heparin cessation and starting a nonheparin anticoagulant. There is no difference in effectiveness or safety among the multiple nonheparin agents used in the treatment of HIT. When a patient with HIT is complicated with a massive pulmonary embolism (PE), initiating a parenteral nonheparin anticoagulant is recommended. Duration of anticoagulation depends on presence of thrombosis. Resolution of thrombocytopenia usually occurs within 7 days, and antibodies resolve 3 months after discontinuation of heparin. Given 5–20% mortality in patients with HIT and significant morbidity, physicians must recognize HIT early and initiate treatment.