There have been many different approaches proposed for the quantitative evaluation of the benefit:risk of a biopharmaceutical product. In this presentation we will discuss various benefit:risk assessment approaches that can be potentially used to meet the needs of global regulatory agencies, health technology assessment organizations and prescribers. Some of the challenges we will address include criteria for comparison of benefit:risk approaches, selection of weights and patient preference, and identification of a subgroup with an enhanced benefit:risk profile.