Cyanobacteria are the Earth's oldest (∼3.5 bya) oxygen evolving organisms, and they have had major impacts on shaping our modern-day biosphere. Conversely, biospheric environmental perturbations, including nutrient enrichment and climatic changes (e.g. global warming, hydrologic changes, increased frequencies and intensities of tropical cyclones, more intense and persistent droughts), strongly affect cyanobacterial growth and bloom potentials in freshwater and marine ecosystems. We examined human and climatic controls on harmful (toxic, hypoxia-generating, food web disrupting) bloom-forming cyanobacteria (CyanoHABs) along the freshwater to marine continuum. These changes may act synergistically to promote cyanobacterial dominance and persistence. This synergy is a formidable challenge to water quality, water supply and fisheries managers, because bloom potentials and controls may be altered in response to contemporaneous changes in thermal and hydrologic regimes. In inland waters, hydrologic modifications, including enhanced vertical mixing and, if water supplies permit, increased flushing (reducing residence time) will likely be needed in systems where nutrient input reductions are neither feasible nor possible. Successful control of CyanoHABs by grazers is unlikely except in specific cases. Overall, stricter nutrient management will likely be the most feasible and practical approach to long-term CyanoHAB control in a warmer, stormier and more extreme world.