Malaria is both an economically and medically burdensome disease taunting people worldwide. Treatments for the disease – transmitted by malarial Aedes and Anopheles mosquitoes infected with Plasmodium – are either temporary or in developmental stages, while rising insecticidal resistance and mosquitoes’ behavioral changes call for a lasting solution to responsibly fight malaria. The application of gene drive (GD) technology – biasedly propagating genetic material into a population using CRISPR/Cas9 – has been suggested. By introducing a sex ratio bias into malarial mosquito populations, or by targeting the mosquito’s interaction with the Plasmodium-parasite, malaria could be eradicated. The design, testing and implementation phases of GDs must, however, be approached with caution, due to the invasive nature of and controversy around the technology. To prevent harmful consequences, the risk management strategy of Safe-by-Design (SbD) was used to compose a set of guidelines for selected SbD Risk Categories. Academic literature and scientist interviews were used to obtain insights of possible risks and to find balance between medical progress and technological threats. Stakeholder involvement was found to be an important part of the GD design process, with a multidisciplinary team of experts, appointed and enforced by international organizations. The team must be held co-responsible for compliance with the guidelines of all four SbD Risk Categories, covering (i) unintended effects on non-target organisms and ecosystems, (ii) horizontal gene transfer (HGT), (iii) pathogenicity and toxicity, and (iv) run-off risk and reversibility. Key findings include previously proposed models, including an inhibitory rock–paper–scissors and a confining split-drive model for GD regulation. After carefully considering the available knowledge and the guidelines necessary for responsible research, I concluded that further research into mosquitoes’ ecosystems, target-specificity, HGT prevention and the theoretical GD models is required.