Water-soluble PbSe semiconductor quantum dots (QDs) with near-infrared absorption of 1100–2520 nm (corresponding to a diameter of 3–13 nm) were synthesized using 2-aminoethanthiol (AET). The oleic acid-stabilizing ligands used in the traditional synthesis of PbSe were exchanged with the 2-AET ligands, which promoted the solubilization of the QDs in an aqueous medium. This occurred due to the attraction of the surrounding water molecules to the exposed amino group, thus allowing the particles to reside in the water environment. The water-soluble PbSe QDs have very narrow size distribution (σ ≈ 4.5–5.5%). Transmission electron microscopy, spectrophotometric measurements, and Fourier transform infrared spectroscopy indicate that the morphology, size, size distribution, and chemical composition of the PbSe QDs remained unchanged during the transfer to an aqueous medium. In conclusion, the ability to synthesize water-soluble PbSe QDs with stable properties and uniform size distribution will allow them to have substantial advantages for biological applications such as biosensors and drug delivery.