Primary immunodeficiency diseases (PIDs) are a heterogeneous group of inherited disorders that cause individuals to be prone to a variety of clinical manifestations, such as infections, autoimmunity, and malignancies. Early diagnosis and adequate treatment of these disorders can reduce morbidity and mortality and provide a relatively high quality of life. In Iran, recent advances in clinical immunology and in the identification of immunodeficiencies have led to reductions in diagnostic delay and severe complications in patients with PIDs. Autosomal recessive and multifactorial types of PID seem to be more common in Iran because of high rates of consanguine marriages and, probably, the genetic background of its ethnic groups. These facts necessitate special diagnostic and treatment approaches, but at the same time reveal an opportunity to observe novel phenotypes and genetic defects.