Yes. Resistance could develop through selection of organisms bearing a genetic change that is not susceptible to the gene drive system, similarly to how resistance arises to frequently used insecticides or drugs. Resistance is potentially a concern because it could prevent the gene drive from spreading and persisting within the target species, and reduce the desired effects of the gene drive system on that target population. In the case of gene drives for public health, this would be problematic if it happened before disease transmission could be eliminated.
For insecticides and drugs, resistance is combatted by switching between different types of products or using combinations of products. However, genetic engineering offers new ways of reducing the possibility of resistance developing in gene drive-modified organisms. Researchers are actively working to find mechanisms that will avoid or delay the development of resistance to gene drive. For example, they are targeting the gene drive system to crucial genes where a genetic change would be detrimental to the organism, and to regions of the target gene that are least likely to change.