Caterpillars-the larval form of butterflies and moths-belong to the order Lepidoptera. Some identified caterpillars from this order have developed venomous defense mechanisms such as irritating hairs and spines to protect themselves from predators. Direct contact to allergenic caterpillars' hairs can cause human disease. Cutaneous lesions following caterpillar envenomation can range from mild localized inflammatory signs and pain to a worsening appearance of vesicles, bullae, erosions, petechiae, necrosis, and ulceration. This review addresses the varied general manifestations caused by venomous lepidopteran exposure with special focus on the adverse cutaneous manifestations and therapeutic options of Megalopyge opercularis, the caterpillar of the flannel moth.