Delusional infestation is an uncommon disorder in which patients have a fixed, false belief (delusion) that they are infested with living pathogens or non-living (inanimate) objects. Patients have abnormal cutaneous symptoms such as itching, biting, or crawling and demonstrate self-destructive behavior to remove pathogens. Some patients’ symptoms may be due to systemic diseases, malignancies, drug abuse, micronutrient deficiencies, etc. Diagnosis and management of these patients present particular challenges to dermatologists and psychiatrists. Patients often resist psychiatric referrals. By treating the patient with, preferably, a second-generation atypical antipsychotic and integrated psychodermatology care, remission is achievable. This review article aims to briefly overview this disabling condition, including its pathomechanisms, clinical presentation, diagnosis, and management. Strategies to establish a strong therapeutic alliance with these patients have been discussed.