This paper analyses and discusses spatial and temporal patterns in the prevalence of major skin diseases (lymphocystis, epidermal hyperplasia/papilloma, ulcers), intestinal parasite Glugea sp., and liver cancer in dab (Limanda limanda) and flounder (Platichthys flesus) in the Dutch section of the North Sea since the mid-1980s. We have attempted to relate disease prevalence trends in both species to chemical contaminant exposure and other relevant environmental factors including fish condition factor, population density, fishing activity, and water temperature. We observed a long-term decline in chemical-related liver cancer in the populations of both species since the early 1990s. Lymphocystis and skin ulcer (flounder only) have also displayed a significant decrease since then. We conclude that the widespread decline in the prevalence of several skin diseases and liver cancer in dab and flounder in Dutch waters in the past two decades is most likely due to the improved water quality and health conditions in this region.