This chapter, Autonomy and Beneficence in Genetic Manipulation, by Claudio S. Cinà discusses the incorporation of genome-editing tools, such as CRISPR-Cas9 and AI-augmented genomics, into surgery. It covers both somatic and germline interventions, with a focus on the ethical challenges between maintaining respect for patient autonomy and seeking beneficent initiatives. Among the main issues discussed are the complexities of informed consent, the protection of data privacy, and the imperative to ensure universal access to health services. The chapter also considers current regulatory regimes, cultural implications, psychological impacts, and the need for environmental responsibility. Concrete real-world scenarios, such as the He Jiankui affair, illustrate the ethical decision-making process and highlight the practical tools available to surgeons. For today’s surgeons, ethical competence in genomic medicine is as relevant as technical skills.