We have developed a versatile, one-step melt synthesis of water-soluble, highly emissive silicon nanoparticles using bifunctional, low-melting solids (such as glutaric acid) as reaction media. Characterization through transmission electron microscopy, selected area electron diffraction, X-ray photoelectron spectroscopy, and Raman spectroscopy shows that the one-step melt synthesis produces nanoscale Si cores surrounded by a silicon oxide shell. Analysis of the nanoparticle surface using FT-IR, zeta potential, and gel electrophoresis indicates that the bifunctional ligand used in the one-step synthesis is grafted onto the nanoparticle, which allows for tuning of the particle surface charge, solubility, and functionality. Photoluminescence spectra of the as-prepared glutaric acid-synthesized silicon nanoparticles show an intense blue−green emission with a short (ns) lifetime suitable for biological imaging. These nanoparticles are found to be stable in biological media and have been used to examine cellular uptake and distribution in live N2a cells.