Recognition of immunodeficiency allows steps to be taken to minimize morbidity and mortality. Immunodeficiency can be secondary to viral infection, most importantly secondary to HIV-1 worldwide, medications, disruption of the usual infection clearance mechanisms, or secondary to a myriad of systemic disorders. Immunodeficiency may also be due to one of the growing list of primary immunodeficiency disorders. In infancy, lymphopenia should trigger an evaluation investigating the possibility of severe combined immunodeficiency. Evaluations of children should be done keeping in mind that normal numbers of lymphocytes are higher in children than in adults, immunoglobulin levels in children are lower than in adults in younger age groups, and antibody production in response to polysaccharide antigens is not usually fully developed in the less-than 2-year-old child.