Cosmetics and ointments utilized for dermatological purposes often bear unintended and sometimes opposing effects of their indicated use. Although there exists various animal and human models of acnegenesis, such as the Mexican hairless dog, the Rhino mouse, and the rabbit ear assay (REA), an elucidative assay that precisely reflects comedogenesis is not yet available. In this review, acnegenic components--i.e., keratinization, androgens, bacteria, sebum and genetics--are examined on an individual basis and correlated to animal models. Current animal models of comedogenesis focus on individual aspects of a multifaceted clinical condition, acne. Presently, the most commonly used assay is the REA, which possesses a hypersensitive response to acnegenic substances compared to human skin; however, this model is unable to accurately depict the acnegenic potential of chemical compounds, and is therefore only valuable for distinguishing absolute negatives. Developing an animal model that is true to the human condition will require further epidemiological evaluation of acne to elucidate the complex condition.