Delusional infestation is a psychiatric condition defined by a fixed belief of infestation despite contrary evidence. Diagnosis includes exclusion of organic etiologies. Treatment with antipsychotics is effective and safe in the majority of patients. Patients are characteristically reluctant to pursue psychiatric evaluation and may resist discussing their disease in psychiatric terms. Strategies to strengthen the provider-patient therapeutic alliance facilitate communication around appropriate treatment. Without antipsychotic medications, patients can become heavy utilizers of care and practice self-destructive behaviors in attempts to clear their perceived infestation.