ABSTRACT: Immunodeficiencies frequently present in the skin antepartum and in the first year of life. Although genetic immunodeficiencies are uncommon, the worldwide incidence of the acquired immunodeficiency human immunodeficiency virus (HIV) is growing. Early diagnosis and treatment of neonatal immunodeficiencies and associated infections result in improved quality of life and longer life expectancy for these patients. In developed countries, improvements in therapy of HIV during pregnancy have resulted in reduced transmission to the neonate. This article reviews the common presentations and therapy of genetic and acquired neonatal immunodeficiencies.