In the past few decades the number of airplanes has increased dramatically and aircraft systems have become increasingly more complex. Under these conditions, the next generation of airplanes will undergo substantial changes and will make significant technical progress to improve operational safety. This vision is entirely consistent with the adoption of Integrated Vehicle Health Management (IVHM) technology which uses merging of interdisciplinary trends to carry out safe and effective vehicle operation. Hitherto, IVHM has made much progress in the realm of maintenance and operation, but little on safety assessment. This paper discusses the issues around how IVHM could be used to aid the operational safety assessment in the aviation industry. Special attention is paid to existing safety assessment methods, and some challenges and promising research directions are highlighted.