An important task for both dentists and pediatricians dealing with patients manifesting different oral lesions is to be able to differentiate changes signaling systemic disease from those appearing without any concomitant serious health problem. In this article, symptomatology of selected primary immune deficiency diseases are discussed with particular emphasis on oral manifestations reported in this group of disorders. Facial, dental, and oral findings compose a constellation of symptoms observed in immunodeficiency diseases. Predisposition to bacterial invasion, cytokine dysregulation, tissue inflammatory process, and necrosis lead to early-onset oral lesions and periodontitis. Developmental abnormalities, periodontal disease, and oral lesions may accompany immunodeficiency and require particular awareness directed toward diagnosis of an underlying disease of the immune system.