This article deals with methods for the estimation of loss of life due to flooding. These methods can be used to assess the flood risks and to identify mitigation strategies. The first part of this article contains a comprehensive review of existing literature. Methods have been developed for different types of floods in different regions. In general these methods relate the loss of life in the flooded area to the flood characteristics and the possibilities for evacuation and shelter. An evaluation showed that many of the existing methods do not take into account all of the most relevant determinants of loss of life and that they are often to a limited extent based on empirical data of historical flood events. In the second part of the article, a new method is proposed for the estimation of loss of life caused by the flooding of low-lying areas protected by flood defences. An estimate of the loss of life due to a flood event can be given based on: (1) information regarding the flood characteristics, (2) an analysis of the exposed population and evacuation, and (3) an estimate of the mortality amongst the exposed population. By analysing empirical information from historical floods, new mortality functions have been developed. These relate the mortality amongst the exposed population to the flood characteristics. Comparison of the outcomes of the proposed method with information from historical flood events shows that it gives an accurate approximation of the number of observed fatalities during these events. The method is applied to assess the consequences for a large-scale flooding of the area of South Holland, in the Netherlands. It is estimated that the analysed coastal flood scenario can lead to approximately 3,200 fatalities in this area.