After the substantial improvements in cure rates for childhood acute lymphoblastic leukemia (ALL) obtained with intensified treatment strategies in the 1970s and 1980s, the last decade has seen slower progress on several fronts. Long-term follow-up has revealed late treatment-related adverse effects and focused attention on risk-targeted therapy to minimize adverse effects in patients at standard risk. Advances in the understanding of the biological features of childhood ALL have provided a platform for the development of such risk-directed protocols. At the same time, salvage of patients who have relapsed has improved such that 5-year overall survival rates are approaching 85%. The United Kingdom Medical Research Council Childhood Leukaemia Working Party has conducted trials of childhood ALL therapy (UKALL protocols) since the late 1960s. Early studies (UKALL I, II, III and V) focused on randomized testing of various aspects of the St Judes' first total therapy protocol. Later studies have confirmed the benefit of intensified therapy (UKALL X and XI), and shown that standard risk patients do not need cranial radiotherapy to prevent central nervous system relapse. UKALL R1 and R2 documented the efficacy of salvage chemotherapy. Improvements in infant ALL outcome have been less impressive and 5-year event free survival is still a disappointing 40%. Future strategies will incorporate more specific risk-directed therapy and greater international collaboration.