Semiconductor quantum dots (QDs), particularly CdSe-core QDs, have shown promise as alternatives to organic dyes for biological labeling due to their bright, photostable fluorescence. However, their potential cytotoxicity remains a concern. This study investigates the cytotoxicity of CdSe-core QDs under various conditions, including processing parameters, exposure to ultraviolet light, and surface coatings. The results indicate that CdSe-core QDs can be acutely toxic under certain conditions, particularly when surface oxidation occurs, leading to the release of free Cd²⁺ ions. Surface coatings such as ZnS and BSA significantly reduce, but do not eliminate, cytotoxicity. The study also demonstrates that CdSe-core QDs can be used for long-term live cell labeling without adverse effects on cell viability, migration, or differentiated function in vitro. However, in vivo applications require careful consideration, as prolonged exposure may lead to cadmium release and toxicity. The findings suggest that surface coatings and processing strategies should be optimized to minimize heavy metal toxicity in biological applications. The study highlights the importance of understanding the mechanisms of QD toxicity and developing strategies to enhance their biocompatibility for both in vitro and in vivo applications.Semiconductor quantum dots (QDs), particularly CdSe-core QDs, have shown promise as alternatives to organic dyes for biological labeling due to their bright, photostable fluorescence. However, their potential cytotoxicity remains a concern. This study investigates the cytotoxicity of CdSe-core QDs under various conditions, including processing parameters, exposure to ultraviolet light, and surface coatings. The results indicate that CdSe-core QDs can be acutely toxic under certain conditions, particularly when surface oxidation occurs, leading to the release of free Cd²⁺ ions. Surface coatings such as ZnS and BSA significantly reduce, but do not eliminate, cytotoxicity. The study also demonstrates that CdSe-core QDs can be used for long-term live cell labeling without adverse effects on cell viability, migration, or differentiated function in vitro. However, in vivo applications require careful consideration, as prolonged exposure may lead to cadmium release and toxicity. The findings suggest that surface coatings and processing strategies should be optimized to minimize heavy metal toxicity in biological applications. The study highlights the importance of understanding the mechanisms of QD toxicity and developing strategies to enhance their biocompatibility for both in vitro and in vivo applications.