Water levels of lakes fluctuate naturally in response to climatic and hydrological forcing. Human over-exploitation of water resources leads to increased annual and interannual fluctuations of water levels, at times far beyond natural amplitudes and/or at altered time schedules. Climate change models predict increased occurrence of extreme events (flooding, extended droughts), which will further magnify the seasonal and multiannual amplitude of water level fluctuations in lakes. A relatively wide literature base already exists for shallow lakes, demonstrating that excessive water level fluctuations impair ecosystem functioning, ultimately leading to shifts between clear-water and turbid states. Evidence is gradually building in the published literature demonstrating that deep (stratified) freshwater lakes also respond adversely to excessive water level fluctuations. Analysis of existing data suggests that at moderate disturbance levels littoral habitats are affected, and hence their biota is also impacted. At further disturbance levels, ecosystem destabilization symptoms are observed, including weakening of keystone species, proliferation of nuisance and invasive species, loss of biodiversity, and increased internal nutrient loading. Ultimately, eutrophication symptoms are manifested, especially large and more frequent cyanobacterial blooms, without increased external nutrient loading. Examples from a range of subtropic and temperate freshwater lakes and reservoirs demonstrate that both top-down and bottom-up processes promote those symptoms. The response of aquatic ecosystems, particularly deep lakes, to water level fluctuations is an under-studied field of crucial importance to the management of water resources, where limnologists have a leading role to play in the near future.