Vaccine is the most effective tool to prevent infectious diseases and to improve the public health. With the advance of modern medicine, the survival rate among pediatric cancer and chronic disease patients treated with immunosuppressive medication has improved greatly. However, immunosuppressant therapy has impact on vaccine-induced immune protection in children. As a result, the immunosuppressive children are in a high risk of developing vaccine-preventable diseases. This article is to review the clinical impact and mechanism of immunosuppressant therapy on vaccine-induced immune protection in children.