Specific antibody deficiency (SAD) is defined as the inability to mount an antibody response to purified Streptococcus pneumoniae capsular polysaccharide antigens in the presence of normal immunoglobulin concentrations and normal antibody responses to protein antigens. In this review, we discuss the difficulties in using presently available testing methods to adequately define SAD. The fact that there are different forms of SADs to pneumococcal surface polysaccharides is detailed. The diagnostic and therapeutic implications of recognizing that, in addition to SAD, there are other forms of SAD in the response to S. pneumoniae polysaccharides are described in detail. The conclusion of this review is that assessment of immunity and therapeutic actions to deal with SADs need to be based on clinical evidence rather than solely on arbitrarily defined antibody responses. (C) 2019 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology