The infundibulum is the funnel-shaped, uppermost epithelial segment of the hair follicle. Thus, as the infundibulum represents a major interface zone of mammalian skin epithelium with the environment and harbors a rich residential microflora, it is not surprising that this area is endowed with a specialized immune system and innate immune defenses. Clinically, the infundibulum is quite important, as it becomes prominently involved in many skin diseases such as acne, infundibular folliculitis and cysts, hidradenitis suppurativa, keratosis pilaris, Fox-Fordyce disease, and a subtype of basal cell carcinoma. Nevertheless, the biology of the infundibulum is only poorly understood, and it remains largely unknown how exactly the infundibulum contributes to skin disease, and how it might be targeted effectively for treating important skin diseases. Several recent studies in mouse models have identified new potential infundibular markers, shed light upon infundibular development and homeostasis, identified infundibular epithelial stem cells, and have implicated the infundibulum in the pathogenesis of additional skin disorders. These recent insights encourage one to systematically re-visit the biology and pathology of the infundibulum, one of the most important, yet least-studied frontiers in mammalian epithelial physiology.