Epidermis has a powerful innate immune system that protects host from bacterial and fungal infections. Within epidermis structural cells, such as keratinocytes and sebocytes, represent immunologically active cells capable to identify and kill invading microbes. These cells recognize highly conserved structures of the pathogens termed Pathogen-Associated Molecular Patterns (PAMPs) by different Pattern Recognition Receptors (PRRs). Activation of PRRs results in the production of effector molecules, such as antimicrobial peptides and pro-inflammatory cytokines/chemokines. These mediators have direct microbicidal effects and attract professional immune cells into the skin. Moreover, recent findings indicate the importance of antimicrobial peptides as effector molecules of innate immunity as well as regulators of acquired immune responses, inflammation and wound repair. Although bacterial involvement is not a primary pathogenic event in inflammatory acne, it is considered to be secondary to the disease process. Thus, given that secondary bacterial colonization can intensify chronic inflammation, it is important to outline the current findings regarding PRR expression and effector molecule secretion in the epidermis. We herein review the role these proteins may play in the pathogenesis of inflammatory acne and the possible effects of the inflammatory infiltrate.