Recent outbreaks of Pfiesteria piscicida and a second known toxic Pfiesteria species have provided a compelling illustration of strong linkages between fish kills and subtle but serious impacts on human health. These two species thus far comprise the toxic Pfiesteria complex (TPC). Toxic strains of TPC species show strong attraction to live fish; toxicity triggered by the presence of fresh materials from live fish; and production of bioactive compounds that cause fish stress, disease and death. They also have a complex life cycle with multiple amoeboid as well as flagellated stages. TPC species are eurythermal and euryhaline, with optima for toxic activity at > 22oC and 15 psu. Their prey span the estuarine food web from bacteria to mammalian tissues. Toxic Pfiesteria outbreaks are known thus far from poorly flushed, nutrient-enriched areas of the Albemarle-Pamlico (epicenter, 88 events, > 1 billion fish affected) and Chesapeake (3 events, 30,000 fish affected) of the mid-Atlantic U.S. TPC species can be strongly stimulated by both N and P enrichments, both directly (organic N, P uptake; and inorganic nutrient uptake by kleptochloroplastidic strains) and indirectly (mediated through algal prey). Water-soluble putative toxin produced by fish-killing Pfiesteria cultures has been partially purified based on c-fos-luciferase reporter gene assay-guided fractionation. This component kills fish and causes a concentration-dependent, prolonged elevation of cytosolic free calcium in GH4C1 pituitary cells and in primary cultures of neurons isolated from rat hippocampus. A hydrophobic toxin component has promoted edema and sloughing of fish epidermal tissue. Human health impacts from contact with water or inhalation of air over areas with actively toxic TPC populations have included respiratory, visual, and neurological impairment, especially severe neurocognitive impairment manifested as mostly reversible short-term memory dysfunction. Moreover, accumulating evidence indicates that these dinoflagellates can cause serious chronic impacts on human as well as fish health.