Various kinds of stimuli-responsive N-isopropylacrylamide copolymers are among an important class of bioengineering materials that have been the subject of many extensive investigations in the field of modern macromolecular bioengineering and biotechnology. These materials are of special interest in the fields of cell and enzyme immobilization, controlled drug delivery and gene delivery, bioconjugation, and protein dehydration process. This review summarizes the main advances published over the last 15 years, outlining the synthesis, structural phenomena, unique properties and application areas of the bioengineering copolymers of N-isopropyl acrylamide with various types of comonomers. These copolymers include linear, end functionalized and crosslinked binary and ternary copolymers, graft and block copolymers exhibiting stimuli-responsive behavior, and reversible phase transitions. Particular attention is paid to the effects of hydrogen-bonding and complexing in copolymerization reactions, the formation of supramacromolecular structures, bioconjugates, physically and chemically crosslinkable copolymers, thermosensitive hydrogels and ion-exchange membrane systems, and other important bioengineering materials. (c) 2007 Elsevier Ltd. All rights reserved.