Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immune deficiency in adults. CVID is characterized by the sequelae of an antibody deficiency syndrome: an impaired terminal B cell differentiation results in hypogammaglobulinemia and susceptibility to recurrent infections by encapsulated bacteria. The clinical course of CVID is complicated by a plethora of systemic immunopathology, including autoimmunity, lymphoproliferation, malignancy and sarcoid-like granulomas. Phenotypic and functional studies in CVID patients revealed multiple abnormalities within the innate and adaptive immune system. The recent description of monogenic defects in ICOS, TACI and CD19 focussed our interest to an impaired T cell-B cell collaboration within the germinal center and intrinsic B cell defects as possible explanations for the etiology of CVID.