Treatment refusal and abandonment is the principal cause of therapy failure in children with cancer in the developing world. A complex interplay of biological, socio-economic and treatment-related factors underlies this problem. Interventions are likely to succeed when they try and address all of these issues simultaneously, as exemplified by the success of twinning programs linking resource-rich and resource-limited countries. Hitherto, there has been no systematic attempt to understand and address this problem in India. Based on the knowledge gained from research in other parts of the developing world, we offer suggestions for dealing with this problem.