Fluorescent semiconductor nanocrystals (quantum dots) have been widely used as a novel class of nanoprobes in biological imaging. Conventional fluorophores, like small organic dyes and fluorescent proteins, have been commonly used for such imaging; however, they show low photobleaching thresholds, and each fluorophore has a defined excitation band and a broad emission band. Although quantum dots offer novel optical properties that overcome the limitations associated with organic molecules, their size and shapes are not uniform and their surfaces are heterogeneous. Consequently, optical properties of quantum dots significantly vary with surface atoms and ligands. To better understand the surface properties of CdSe-based quantum dots, we studied their optical properties as a function of shell composition, ligand, and surface facet. We have developed synthetic methods that enable the epitaxial growth of shell over zinc-blende CdSe quantum dots. Then, we have characterized surface ligands using secondary ion mass spectrometry. In addition, we have studied the coordination of trioctylphosphine oxide, sulfide, and selenide, to Cd2+ and Zn2+ using collision-induced dissociation mass spectrometry. Moreover, we have examined ligand- and shell-dependent blinking of quantum dots at the single-molecule level and presented a two-competing channel model for blinking. Based on our understanding of surface-dependent optical properties of nanocrystals, we have devised a binary amine–phosphine ligand system that passivate electron and hole traps on the surface, thereby yielding bright CdSe quantum dots without inorganic shells. For biological applications, we have introduced bioconjugation chemistry for hydroxylated quantum dots, which enables background-free detection of biomolecules. Thus, hydroxylated quantum dots can be applied to highly sensitive fluorescence detection of DNAs and proteins without nonspecific binding to biosurface in a wide range of pH. Most recently, we have studied chemical and photochemical etching methods to find a way to control the size of quantum dots, nanorods, nanowires, tetrapods, and nanoplatelets. Nanohemistry related to surface passivation, fluorescence blinking, bioconjugation, and chemical and photochemical etching of nanomaterials will be presented.