<p>Dermatological delusional disorders, such as delusional infestation (DI), are a unique type of psychosis in which the patient experiences specific delusions, such as parasites or inorganic materials that come out of their skin. Originally, this type of “encapsulated psychosis” was thought to be unresponsive to antipsychotic agents. However, over the past half a century, several medications with antipsychotic properties have been found to be effective in the treatment of these conditions in the USA, especially pimozide and risperidone. Despite effective treatments, several challenges may arise for clinicians in successfully treating patients with these conditions. These challenges include selecting an efficacious medication and skillfully practicing diplomacy and empathy while guiding patients toward effective management. Navigating interactions with patients with DI and their frequent denial of a psychiatric component to their condition often poses additional challenges to patient-provider rapport and proper and timely management. In the USA, many patients with DI are opposed to trying the conventional approach of psychiatric care and immediate trial of antipsychotic medications. This manuscript represents a single-center psychodermatology perspective on managing dermatologic delusional disorders. This article synthesizes clinical experience from a US clinic and situates that experience within the available evidence. High-quality comparative data are limited. Therefore, this paper highlights pragmatic engagement strategies, pharmacotherapy principles, essential safety monitoring, and research priorities. Experience-based recommendations are clearly labeled as such.</p>