Nanogels are nano-sized networks composed of hydrophilic or amphiphilic polymer chains. Unloaded nanogels in a swollen state contain considerable amount of water. Nanogels can readily incorporate oppositely charged low molecular mass drugs or biomacromolecules such as oligonucleotides, siRNA, DNA and proteins, which bind with the nanogel’s ionic chains and phase separate within the finite nanogel volume. Such loading is usually achieved spontaneously through electrostatic, van-der Waals and/or hydrophobic interactions between the agent and the polymer matrix. As a result, nanogels collapse forming stable nanoparticles, in which therapeutic agent becomes entrapped. The functional groups at the nanogel surface can be additionally modified with various targeting moieties for site specific drug delivery in the body. Various nanogels were shown to deliver their payload inside cells and across biological barriers. Such nanogels exhibit high stability and protect biological agents from degradation by cell’s metabolic systems. Overall nanogels demonstrate excellent potential for systemic drug delivery due to their high loading capacity, high stability, and responsiveness to environmental factors, such as ionic strength, pH, and temperature that are unprecedented for common pharmaceutical nanocarriers.