Introduction: Gene therapy encompasses a diverse array of genetically engineered products in biomedical research. As novel products continue to gain regulatory approval, institutions will be challenged by translating research processes into the clinical environment. This article will provide a summary of the 5 in vivo viral-based therapies that have been approved or are under review in the United States or European Union and discuss the development of biosafety handling practices in the clinical setting. Discussion: Commercially approved gene therapies utilize adeno-associated viral vectors, lentiviruses, and modified herpes simplex viruses for genetic manipulation. Health care personnel must understand the location of the genetic manipulation, ex vivo or in vivo, in order to develop safe work practices when handling the products. Occupational exposure to a viral agent could lead to risks of infection or acquired immunity. Institutions must merge biosafety and hazardous drug handling standards in order to develop safe handling procedures for clinical care. Conclusion: As biotechnology continues to advance, so will the challenges of incorporating novel therapies into the clinical setting. Health systems must educate themselves on the current recommendations and maintain competency of this evolving science to ensure the safety of patients, families, and staff in the clinical environment.