This article analyzes the current recommended practices and evidence in the immunization of pediatric 'special risk groups'. Special risk group patients are at higher risk of vaccine-preventable diseases and hence require additional strategies to maximize protection against these diseases. The special risk groups include those with an underlying chronic disease, some of whom are on immunosuppressive therapy to treat that condition. The article uses four special risk groups (acute lymphoblastic leukemia; preterm birth; juvenile idiopathic arthritis; and inflammatory bowel disease), to highlight the management considerations and potential vaccination strategies. The risks, benefits and timing of vaccination in the setting of immunosuppression require detailed discussion with treating clinicians, in particular the use of live-attenuated vaccines. The immunogenicity of vaccines in these special risk groups helps provide the evidence base for their immunization guidelines. Protection can include 'cocooning' (i.e., ensuring appropriate immunizations within the immediate family; e.g., varicella, influenza and pertussis vaccination). Improving timeliness and minimizing missed opportunities to vaccinate individuals with these special risk conditions will also optimize protection from vaccine-preventable diseases.