Small molecule tyrosine kinase inhibitors (TKIs) are potent anti-cancer targeted therapies. TKIs are considered safe and efficacious therapeutic modalities, and are generally tolerated well. However, they are associated with certain side effects including hematologic toxicities such as anemia, macrocytosis, neutropenia, thrombocytopenia, hemolytic anemia, bone marrow aplasia and necrosis. Thrombotic microangiopathy, arterial thromboembolism and splenic infarction can also occur following treatment with TKIs. Cytopenias are the most common adverse effects associated with these agents, and other hematologic toxicities are not frequent. It is essential for clinicians to monitor patients closely, and recognize those side effects as early as possible, in order to improve efficacy of small molecule TKIs and optimize outcomes. This article summarizes hematologic toxicities associated with the commonly used small molecule TKIs. It also provides practical strategies for the management of these toxicities.