Nanoparticles offer several advantages in drug delivery. The progress in the development of nanoparticles for biomedical applications has moved from the first generation nanoparticles to the fifth generation nanoparticles and the transitions reflect their increasing versatility in biomedical applications. Polymeric nanoparticles are prepared mainly by two methods: dispersion of preformed polymers and in situ polymerization of monomers and macromonomers. Polymerization induced self-assembly (PISA) for the fabrication of nanoparticles is believed to be a better strategy than nanoparticle fabrication from preformed polymers (ease of tethering targeting ligands to the corona of the nanoparticles and unlike PISA, creation of nanostructures via self-assembly of block copolymers is performed in low concentrations. Dispersion polymerization involves one-pot synthesis of nanoparticles. RDRP processes such as atom transfer radical polymerization, reversible addition-fragmentation chain transfer polymerization and nitroxide mediated polymerization have revolutionized polymer synthesis by providing polymer chemists with powerful tools that enable control over architecture, composition and chain length distributions. The technique for the fabrication of nanoparticles by dispersion polymerization (PISA) at ambient temperature was described with examples from our laboratory involving organic redox initiated polymerization using the FDA approved biodegradable polymers. Computer optimization is useful in understanding the factors that ensure optimized properties of drug-loaded nanoparticles.