Hyperviscosity syndrome (HVS) is considered an oncologic emergency. In this review, we describe the pathophysiology, clinical presentation, diagnosis, and treatment of this life-threatening condition. The most common etiology of HVS is hypergammaglobulinemia, such as Waldenström macroglobulinemia. Other causes include bone marrow hyperproliferative states, autoimmune diseases, and human immunodeficiency virus infection. The presence of mucosal and specifically bilateral nasal bleeding, along with neurologic and ophthalmologic symptoms, should raise suspicion for HVS, but the condition can affect principally all organ systems. Fundoscopic examination is important when evaluating patients with HVS. The mainstays of treatment of HVS are supportive care, plasmapheresis, and chemotherapy.