River floodplains are sites of extremely high environmental and ecological value due to high biodiversity. Floodplain lakes (FPLs) are essential parts of complex floodplain ecosystems’ biological and hydro-chemical processes. Clear seasonal cycles, determined by the regime of the parent river and closely linked to climatic conditions, are observed in these lakes. Both the quantity and the quality of water are determined by the functional phases of a floodplain lake; limnophase, when the lake is isolated from the river, and potamophase (inundation), when the floodplain lake is overflowed by the river waters. These phases highly modify lake bathymetry, water balance, chemistry, and biology. Human pressure, mostly dam construction and land use changes, alter the frequency, duration, and intensity of natural cycles of inundation. The majority of large rivers in the Northern Hemisphere have been impacted by human activity. Floodplain lakes are also affected by continuous climate change, due to the alterations of the hydrological regimes. Cyanobacterial blooms in floodplain lakes are often characterized by high qualitative and quantitative annual and long-term variability. The main forces driving cyanobacterial blooms can be found in the flooding dynamics and intensity influencing hydraulic residence time and the concentration of biogenic compounds in lake water. Cyanotoxin production and seasonal dynamics in floodplain lakes have been rarely studied, particularly in connection with the hydrological regime. Moreover, the effects of cyanobacterial blooms and their toxicity to organisms inhabiting floodplain lakes, connected rivers, and floodplains are poorly understood. Therefore, knowledge of the processes controlling floodplain lakes’ ecological conditions is crucial to implementing water management and restoration practices, protecting those fragile and precious ecosystems from degradation and possible extension.