Although it is well-established that children undergoing allogeneic stem cell transplants and treatment for leukemia should be offered prophylaxis against Pneumocystis jirovecii pneumonia, the risk for children with solid malignancies is less certain. This guideline has been developed with the aim of standardizing practice and optimizing the benefit versus risk of prophylactic medication in this group of patients. P. jirovecii pneumonia has a high mortality rate even with prompt antimicrobial treatment. Since prophylaxis with co-trimoxazole is safe, effective, and inexpensive, we suggest that all children with malignancies undergoing immunosuppressive therapy are offered prophylaxis unless there are clear contraindications.