Over 80% of children with cancer live in low and middle-income countries where survival rates are much lower than high-income countries. Challenges to successful treatment of paediatric cancers in these countries include late presentation, malnutrition, failure to complete treatment and less-intense supportive care leading to increased treatment-related mortality and the need to reduce the intensity of treatment. Clinical trials can contribute to improved care and survival by providing objective information on the number of patients treated, accuracy of diagnosis, causes of treatment failure and the efficacy of specific interventions. Clinical trials can also help to build capacity (salary support and training), improve facilities (equipment) and fund treatment or essential associated costs (social support, nutritional support and follow-up care). In this article, we discuss our experience with clinical trials in Malawi and sub-Saharan Africa with emphasis on the treatment of children with Wilms tumour.