Hydroxyethyl starch (HES) is widely used for fluid management in broad populations of patients, particularly in the surgery and intensive care settings. Pruritus, often manifested as pruritic crises, is increasingly being recognized as a common major adverse effect of HES administration. This iatrogenic form of pruritus is frequently severe and protracted with a serious negative impact on patient quality of life, including sleep disturbance, disruption of daily routine and mental distress. Such pruritus is generally refractory to available therapies and can persist for up to 12-24 months. All currently clinically available HES solutions entail the risk of pruritus, including those of diverse molecular weights and substitutions. Although dose dependent, HES-induced pruritus nevertheless can often be provoked by relatively low routine doses. The pathophysiological basis for pruritus is the widespread tissue deposition of HES, prominently in macrophages. HES tissue deposits are long lasting and sometimes massive. Usually several weeks elapse between HES exposure and the onset of pruritus. Consequently, it is important to inquire about prior HES exposure in the diagnostic evaluation of pruritus sine materia. Awareness about the scope of the pruritus problem needs to increase among physicians administering HES. Well-designed clinical outcome studies are needed to assess more fully the incidence, dose dependency and mechanisms of pruritus with particular HES solutions.