This chapter reviews the implications of Loss and Damage (L&D) for decision-making with a special focus on the role of the physical sciences for decision support. From the point of view of climate science, the question regarding the estimation of losses and damages associated with climate change can be thought of in terms of two temporal scales: the present and the future. In both cases the aim is to establish the links between human-induced changes in climate and climate variability, the probability of occurrence of extreme meteorological events (e.g., rainfall), and the resulting hazard that causes losses and damages (e.g., flood). We review the approaches used to assess the hazard component of risk, with a special emphasis on identifying sources of uncertainty and the potential for providing robust information to support decision-making. We then discuss tools and approaches that have been developed in the context of Climate Change Adaptation (CCA) to deal with uncertainty from climate science in order to avoid a ‘wait and see’ mentality for decision-making. We argue that these can be applied to some parts of L&D decision-making, in the same way as suggested for CCA, since the challenges presented by the need to reduce and manage climate change losses and damages are not very different from the ones presented by the need to adapt to climate change and variability. However additional challenges for decision-makers, particularly in the context of the underlying science, are posed by the compensation and burden-sharing components of L&D for climate impacts that are beyond mitigation and adaptation’s reach.