Since the mid-1980s, fish-killing blooms of Prymnesium parvum spread throughout the USA. In the south central USA, P. parvum blooms have commonly spanned hundreds of kilometers. There is much evidence that physiological stress brought on by inorganic nutrient limitation enhances toxicity. Other factors influence toxin production as well, such as stress experienced at low salinity and temperature. A better understanding of toxin production by P. parvum remains elusive and the identities and functions of chemicals produced are unclear. This limits our understanding of factors that facilitated the spread of P. parvum blooms. In the south central USA, not only is there evidence that the spread of blooms was controlled, in part, by migration limitation. But there are also observations that suggest changed environmental conditions, primarily salinity, facilitated the spread of blooms. Other factors that might have played a role include altered hydrology and nutrient loading. Changes in water hardness, herbicide use, system pH, and the presence of toxin-resistant and/or P. parvum-inhibiting plankton may also have played a role. Management of P. parvum in natural systems has yet to be attempted, but may be guided by successes achieved in small impoundments and mesocosm experiments that employed various chemical and hydraulic control approaches.