Semiconductor nanocrystals, also known as quantum dots (QDs), possess unique optical properties that make them useful as fluorescent probes or traceable nanocarriers for in vivo applications ranging from imaging to theranostics. The surfaces of QDs can be conjugated with biomolecules to enable in vivo targeted imaging and drug delivery. These unique capabilities and qualities of QDs have made them a powerful platform that can help to reveal important biological insights. Ultimately, they may also provide unique benefits in clinical diagnostic and therapeutic applications. However, progress toward clinical applications has been delayed by concerns about the potential toxicity of QDs. Much of the QDs community has been hesitant to work toward clinical applications, based on reports demonstrating release of toxic heavy metal ions from degradation of QDs in cell culture studies. In addition, photoexcited QDs have been shown to generate reactive oxygen species that are highly toxic to cells. On the other hand, in small animal studies, bioconjugated QDs did not have any observable ill effects at concentrations appropriate for in vivo imaging applications. Thus, conclusions drawn from in vitro and in vivo studies remain somewhat contradictory and do not yet provide a sound basis for confident prediction of in vivo toxicity in humans.