Quantum dots (QDs) have rapidly emerged as an attractive alternative to conventional organic fluorophores in a variety of biological imaging applications. Their improved photostability allows for long-term dynamic imaging of cellular processes and their narrow, size-tunable emission permits unprecedented multiplexing capabilities. Additionally, the inherent brightness of core/shell QDs, with quantum yields capable of exceeding 85%, provides increased sensitivity for both diagnostic screening and single molecule tracking applications. To date, the primary focus of research in this field has been directed towards modifying the surface chemistries of the QDs to introduce biological specificity while, at the same time, limiting nonspecific cellular interactions. As such, biomolecules such as antibodies, peptides, streptavidin and biotin have all been conjugated to QDs and been used to demonstrate specific labeling of cellular targets. Additionally, polyethylene glycol (PEG) modification of the QD surface has been shown to limit nonspecific interactions. The use of small molecule QD-conjugates has also been demonstrated as an effective means for targeted labeling of membrane associated receptors. This approach introduces specificity via ligand-receptor interactions, resulting in a highly modular system which is easily modified to interrogate a wide variety of cellular targets. This article provides a comprehensive review of the current status of QD imaging applications in biological systems with a particular emphasis on the design and application of small molecule nanoconjugates.