Engineered nanomaterials are used globally in biomedical, electronic, and optical devices, and are often discarded into the environment. Cell culture experiments have shown that many inorganic nanoparticles are toxic to eukaryotic cells. Here, we show that populations of eukaryotic cells can evolve to survive chronic exposure to toxic CdSe semiconductor quantum dots (QDs). We grew yeast Saccharomyces cerevisiae for 24 days in liquid medium containing QDs prepared daily at half the minimum inhibitory concentration (MIC50) of the progenitor yeast cells. After 24 days, the cells grew normally under constant exposure to QDs. We concluded that these cells evolved to resist QD toxicity. Surprisingly, when we removed QDs from the growth medium, some of the evolved cells grew poorly, i.e., they grew better in the presence of QDs. Finally, genetic analysis confirmed that the ubiquitin ligase gene bul1 was mutated in the evolved cells, which suggests that this gene may be implicated in increased CdSe QD tolerance. This study shows that chronic exposure to QDs can exert selective pressure causing irreversible genetic changes leading to adaptation.