Streptococcus pneumoniae is an important cause of morbidity and mortality worldwide, it is responsible for invasive pneumococcal disease (IPD) (e.g. meningitis, bacteremic pneumonia and bacteremia) and non-IPD (e.g. pneumonia, acute otitis media, and sinusitis). IPD is preceded by nasopharyngeal colonization with high incidence of disease among young children, the elderly, persons with underlying medical conditions and immunocompromised hosts. The term "immunocompromised host" is generally applied to a variety of patients with various immune defects. The factors that contribute to the development of IPD include host immunity (specific and innate), genetic and environment. Specific defects in host responses to pneumococcal infections may due to very young age, deficiencies in levels of antibodies and complement factors, and splenic dysfunction. The combinations of these defects contribute to the increased rates of IPD. The immunocompromising and other conditions that predispose to pneumococcal disease were described.