We present a review of stimuli-responsive smart PEGylated nanogels and their biomedical applications. We describe the synthesis and characterization of stimuli-responsive PEGylated nanogels composed of a cross-linked poly[2-(N,N-diethylamino)ethyl methacrylate] (PDEAMA) core and PEG tethered chains that bear a carboxylic acid group as a platform moiety for the installation of bio-tags. In addition, PEGylated nanogels show unique properties and functions in synchronizing with the reversible volume phase transition of the PDEAMA core in response to various stimuli, such as pH, ionic strength and temperature. We list some of the biomedical applications of the nanogels, including endosomolytic agents for nonviral gene delivery, drug delivery carriers, nanoreactors, and skin-specific nanocatalysts for reactive oxygen species (ROS). (c) 2007 Elsevier Ltd. All rights reserved.