This concluding section of the series will evaluate the role of host environment in the development of thromboembolism (TE) in children with acute lymphoblastic leukemia (ALL). The available evidence suggests that TE in association with childhood ALL is a multifactorial entity resulting from the interaction of the disease, chemotherapy and its effects, and possible prothrombotic states inherent to the host. The few studies conducted so far in children with ALL have reported wide variability in the prevalence of prothrombotic defects and its impact on the risk of TE. The prevalence of prothrombotic defects varies in different ethnic population. Since different ALL therapy studies use different chemotherapeutic agents in various dosage and combination, it is important that every major study group assesses the risk of TE, including the prevalence of prothrombotic defects, within their therapy plan. This will help to identify the population at risk for TE and for thromboprophylaxis, if indicated.