The primary antibody deficiency syndromes are a group of relatively rare disorders characterized by an inability to produce efficient antibody responses, resulting in clinically agammaglobulinemia in affected individuals. Most of them are caused by mutations in genes involved in B cell differentiation. They commonly present with recurrent infections due to encapsulated bacteria. Treatment of primary antibody deficiencies involves immunoglobulin replacement therapy with appropriate antibiotic therapy. However, diagnostic delay in these disorders remains a problem. In this article, we will discuss the pathogenesis, diagnosis, and treatment of primary antibody deficiency syndromes, with some attention to recent advances in this field.