Despite the greatly improved treatment regimes for childhood acute lymphoblastic leukaemia (ALL) in general, resulting in long-term survival in approximately 80% of cases, current therapies still fail in >50% of ALL cases diagnosed within the first year of life (i.e. in infants). Therefore, more adequate treatment strategies are urgently needed to also improve the prognosis for these very young patients with ALL. Here we review the current acquaintance with the biology of infant ALL and describe how this knowledge may lead to innovative therapeutic approaches.