B-lymphocyte development is essential for production of functional antibody and humoral immune responses. The mechanisms that regulate this process are complex and tightly regulated. Defects in nonredundant components of this pathway lead to a clinical and immunologic syndrome of congenital agammaglobulinemia with absence of B-cell development. X-linked agammaglobulinemia (XLA) was the first of these conditions to be described and is the most common cause of congenital agammaglobulinemia. In 1993, abnormalities in the Bruton's tyrosine kinase (BTK) gene were shown to be the cause of XLA. A considerable amount of research has since been dedicated to understanding the genetic basis and molecular pathogenesis of the disease.