Primary immunodeficiencies are challenging in primary care settings, where clinicians often encounter patients with a history of recurrent infection. With advances in diagnostics and therapeutics, these disorders have been better understood and more successfully treated, yet their prognosis depends on early recognition of the disorder and initiation of the appropriate management. Because the primary care physician is most often the first physician encountered by a patient with immunodeficiency, primary care practitioners should be familiar with these rare but important disorders. This article provides an overview of the diagnosis and treatment of primary immunodeficiencies and two of the most common primary immunodeficiencies: common variable immunodeficiency and selective IgA deficiency.