Pruritus is a sensation that emanates from the skin and is transferred through peripheral nerve fibers to the central nervous system. It is easily understood that primary skin disorders, such as atopic eczema, skin dryness, psoriasis, and urticaria, can elicit pruritus. However, certain systemic diseases can cause chronic pruritus, which has a significant effect on the patient's quality of life. In this rostrum we provide an overview of the characteristics, pathophysiology, and mechanisms of pruritus of major systemic underlying diseases, including end-stage renal disease, cholestatic liver disease, endocrine/metabolic diseases, and hematologic/lymphoproliferative diseases.