Fluorescence imaging is a commonly used approach for sensitive, non-invasive, high resolution imaging of live cells and organisms. The full potential of this approach, however, has not been realized due to restrictions imposed by routinely used organic fluorophores. Use of inorganic fluorescent nanocrystals, quantum dots (QDs), provides an opportunity to better realize the potentials of live cell fluorescent imaging. A prerequisite to the use of QDs for cellular and biomedical imaging, however, is developing approaches for labeling live cells with these reporters and establishing the safety of these reporters for imaging live cells and organisms. Here we present a variety of approaches to efficiently tag molecules and live cells with QDs and have used these methods for the long-term tracking of multiple populations of cells during growth and development. Using these approaches we demonstrate that QD-labeling has no detectable effects on either the physiology of the cells or the organism in which they reside. This establishes QD as a suitable fluorescent probe for both live cells and in vivo imaging.