The flounder (Platichthys flesus) is a flatfish that inhabits marine coastal environments, especially estuaries. It is an alternative quantitative biological indicator to the common marine mussel (Mytilus spp.), which is currently used as a sentinel species to monitor chemical contamination in numerous monitoring programmes. Findings from two decades of monitoring cadmium (Cd) and mercury (Hg) using both sentinel species in the Seine Estuary (France) are reported. For comparison, time-series of water concentrations for the same two metals at the mouth of the River Seine are given. Cd concentrations in the liver of the fish and in the soft tissue of mussels show similar temporal trends, consistent with the major temporal variations of Cd concentrations recorded in river water and with changes in industrial discharge of Cd (phosphogypsum waste) within the Seine Estuary. On the other hand, Hg concentrations in the muscles of flounders show temporal variations with no link to that observed in mussels or fluvial Hg contributions, which are in fact nearly covariant. It is concluded that optimization of the use of flounders as sentinel organisms for monitoring temporal trends of metal contamination in estuarine environments requires in-depth knowledge of its ecology within the area studied. An adapted sampling strategy based on this knowledge should provide results that are easier to interpret.