Byrne served as the first EU Commissioner for Health and Consumer Protection from 1999 to 2004. He is a barrister by training and spent 30 years practicing at the Irish Bar. He became a Senior Counsel in 1985 and was appointed Attorney General of Ireland in 1997. In 1998 he was one of the negotiators of the Good Friday Agreement.
During his period in office as commissioner he sponsored the first EU laws on tobacco control and signed the Framework Convention on Tobacco Control (FCTC) on behalf of the European Union in May 2003. Food safety was part of his portfolio in DG SANCO when over 80 pieces of legislation were adopted by the Commission and made law by the European Parliament and Council of Ministers, most notably the General Food Law establishing the European Food Safety Authority (EFSA). Because of widespread concern relating to global communicable diseases such as SARS and avian influenza he also established the European Centre for Disease Prevention and Control (ECDC). Other initiatives sponsored by him included the conferring of rights on patients to receive cross border healthcare in all EU member states and a forum on the pharmaceutical industry directed towards identifying measures to improve the effectiveness and competitiveness of the pharmaceutical industry and the enhancement of access to medicines for patients.
On retirement from the Commission in 2004 he was appointed a Special Envoy of the WHO to give political leadership to the adoption of the International Health Regulations (IHR) designed to combat global communicable diseases. The IHR was adopted at the World Health Assembly in 2005.
Following his retirement from the WHO, he joined the boards of a number of public companies, including DCC Plc where he was the Deputy Chairman and senior independent director (SID) and Kingspan Plc where he was also the SID.
Currently, he is co-chair of the Brussels based European Alliance for Personalised Medicine (EAPM) and is a member of the Scientific and Ethics board of BBMRI-ERIC, the pan-European research infrastructure of biobanks and biomolecular resources. He also serves as a member of the Council of the Royal College of Physicians of Ireland where he was conferred with an honorary Fellowship of the Faculty of Public Health. He is an honorary Fellow of the Royal College of Physicians of London and has been conferred with an honorary Doctorate of Laws by the National University of Ireland. He is Chancellor emeritus of Dublin City University.