This article discusses stimuli-responsive poly(ethylene glycol) (PEG)-coated (PEGylated) nanogels and their biomedical applications. Preparation and characterization of stimuli-responsive PEGylated nanogels composed of a crosslinked poly(2-[N,N-diethylamino]ethyl methacrylate) (PEAMA) core and PEG tethered chains are initially described. Stimuli-responsive PEGylated nanogels show unique properties and functions in synchronizing with the reversible volume phase transition of the PEAMA core in response to the extracellular pH (7–6.5) of a tumor environment as well as endosomal/lysosomal pH (6.5–5.0) and temperature. We list several biomedical applications of stimuli-responsive PEGylated nanogels, including 19F magnetic resonance spectroscopic imaging (MRS/I) probe to visualize acidosis (tumor tissue), intracellular drug and siRNA delivery, antennas for cancer photothermal therapy and apoptosis probe for monitoring response to cancer therapy. Thus, stimuli-responsive PEGylated nanogels can be utilized as smart nanomedicines for cancer diagnostics and therapy.