Delusional infestation (DI), also known as delusional parasitosis, consists of a patient's strong belief that he or she is infested with a nonliving substance or living organism despite lack of medical evidence to support this belief. The most commonly reported sources of infestation include insects, fibrous strands, worms, and scabies. DI is predominantly seen in women and older patients. This disorder has a variable course and prognosis in patients. DI can be a primary psychiatric problem, or secondary to underlying medical conditions or other psychiatric disorders. It has been proposed that DI presents along a spectrum that includes four categories: overvalued concern of infestation, somatoform preoccupation, delusional state, and terminal delusional state. Management depends on the patient's category at presentation. The diagnostic approach for DI involves a thorough evaluation that can rule out medical conditions that underlie the patient's symptoms. This includes obtaining a detailed history, physical exam, and ordering laboratory tests. Treatment for primary DI includes both first and second-generation antipsychotics. Secondary DI treatment depends on the etiology. The prognosis of patients with DI is difficult to predict due to various factors including level of insight, underlying psychiatric conditions, and medication adherence. It is important for the physician to maintain a therapeutic relationship with the patient in order to properly address the patient's concerns.