In recent decades, the steadily increasing worldwide use of different modeling substances for esthetic purposes has increased the risk of numerous complications affecting several tissues. Complications range from local to systemic alterations triggered by an autoimmune inflammatory response, and these can involve the peripheral nervous system. Early detection of this condition is fundamental to avoiding irreversible damage to these neural structures. A multifaceted approach to diagnosis—which includes serological, imaging, and neurophysiological investigations—is required, followed by a multidisciplinary approach to treatment. However, the literature on peripheral nerve impairment that is caused or triggered by modeling substances remains scarce, and no published guidelines exist. In this chapter, we review the anatomical basis of these nerve injuries, the pathophysiological processes behind them, and the clinical spectrum with which patients present. We then provide recommendations about how this poorly understood condition should be managed.