Defects of antibody production are the most common of the primary immune defects of man. While these defects have been described in clinical terms for more than five decades, in most cases, the pathogenesis is still poorly understood. The most common clinically important of these is common variable immune deficiency. However there is no strict definition of this defect and the criteria for initiating immune globulin therapy are not standardized, leading to wide variation in treatment practices. In addition there has been no clear means to adequate assess progression of lung disease or elucidate the causes of progressive pulmonary inflammation found in some subjects. Moreover, there are still questions such as what are the best predictors of chronic lung disease and how can we prevent this disorder. Other complications such as autoimmunity, granulomatous disease, gastrointestinal inflation, are similarly poorly understood although treatment with various biological agents has been used with some success. A few bio-markers for assessing clinical and immunologic status have been proposed, and some have proved to be useful, but additional methods to gauge the benefits of therapy, predict outcomes, and harmonize treatment practices are needed. Aside from Ig replacement, additional means of prevention of lung disease may need consideration to reduce lung damage apart from prophylactic antibiotics. These might include using macrolides as anti-inflammatory agents, inhaled corticosteroids, bronchodilators, mucolytics or mechanical or rehabilitative respiratory methods.