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Cyanobacterial harmful algal blooms (cHABS) exist as part of a complex ecosystem which includes interactions with both bottom-up (abiotic) and top-down regulators (biotic). Western Lake Erie (Laurentian Great Lakes) is prone to cHABs dominated by Microcystis spp. that often yield microcystin toxin concentrations exceeding the federal EPA recreational contact advisory of 8 μg L-1. Planktothrix agardhii dominates the cHAB community in Sandusky Bay, Lake Erie (USA) from May through September. Here we discuss three studies that focus on the effect of top-down regulators on the annual cyanobacterial harmful algal blooms (cHABs) in the open waters of western Lake Erie and Sandusky Bay as model systems for similar blooms in other regions. Whereas many studies have focused on the factors contributing to the establishment and persistence of cyanobacterial harmful algal blooms (cHABs), this dissertation outlines some of the few studies that have examined bloom pathogenesis. Viral attack on cHABs may contribute to changes in community composition during blooms as well as during bloom decline, yet loss of bloom biomass does not eliminate the threat of cHAB toxin concentrations. Rather, it may increase risks to the public by delivering a pool of dissolved toxin directly into water treatment utilities if the dominating Microcystis spp. is capable of producing microcystins. In addition to viral attacks, chytrid fungi infect cyanobacteria and stimulate food web interactions through manipulation of previously hard to digest filaments and the release of nutrients to support heterotrophic microbes. Infections by the isolated chytrids were specific to Planktothrix planktonic species and were not found on other filamentous cyanobacterial taxa present in Sandusky bay. Even amongst the potential P. agardhii host strains, individual chytrid isolates had different degrees of infectivity and showed preference for different host isolates, suggesting possible ecological partitioning even within the same sample population. Finally, while Planktothrix-specific chytrids have been isolated from bloom events, enumerating chytrids and determining host-pathogen relationships through environmental sampling had yet to be broadly investigated. Planktothrix-specific chytrids were found to be present throughout the bloom season across several years and were occasionally at high enough densities to exert parasitic pressure on their hosts. Taken together, these studies highlight the lesser studied top-down interactions found within cHABs and aim to serve as a starting point for future human health in regards to cyanobacterial toxin release and community ecology projects.