Hyperleukocytosis is characterized by rapid cell turnaround (mature and immature) with peripheral blood white blood cell count (WBC) exceeding 100,000 × 109/L in association with a malignant clone. High WBC count can lead to several lethal complications of which symptomatic leukostasis, disseminated intravascular coagulation (DIC), and tumor lysis syndrome (TLS) are predominant. Untreated symptomatic hyperleukocytosis portends poor prognosis, reflecting the aggressive nature of the biologic drivers behind this entity. In managing hyperleukocytosis, aggressive supportive care measures, leukapheresis, and hydroxyurea could be utilized until completion of diagnostic workup and as a bridge to definitive therapy. Metabolic, hematologic and coagulation abnormalities need to be frequently scrutinized and rapidly corrected to prevent avoidable complications while disease biology targeting therapies alter treatment trajectories to improve patient outcomes.