Platelet transfusion therapy has become an integral part of the treatment of patients with hematological and solid tumor malignancy receiving chemotherapy. Since its introduction almost 60 years ago, several advances and refinements have been introduced in the collection, storage, and administration to improve the safety and efficacy of platelet transfusion. This review summarizes the current practice and clinical approach to patients with thrombocytopenia. Existing evidence-based guidelines for appropriate platelet transfusion is reviewed.