Diffuse pontine tumors are highly lethal and conventional therapy with irradiation provides long-term survival to a very small proportion of the patients. We have reported promising results using high-dose chemotherapy with autologous stem cell rescue in patients with recurrent high-grade astrocytomas in other anatomic locations, but our results and those of others have been very discouraging in children with brain stem tumors. Alternative strategies need to be developed for this highly lethal disease.