Primary immunodeficiency diseases are rare disorders characterized by quantitative or qualitative defects in cells or components in the immune system, resulting in a high degree of susceptibility to various types of infections. During differentiation, stem cells undergo a series of discrete steps, governed by a large number of different genes. Mutations/deletions in these genes will result in a block in differentiation of the affected cell lineage(s), leading to immunodeficiency. To date, more than 150 different types of disorders have been described. In this review, we will focus on novel findings in antibody deficiency syndromes.