Microcystis sp. are ubiquitous and highly prevalent Cyanobacteria found in freshwater ecosystems. They are known for episodic, large-scale proliferations known as “blooms”, which are driven by factors such as elevated nitrogen and phosphorus concentrations, enhanced water column stability, and increased temperatures. Microcystis sp. are infamous for producing a class of potent hepatotoxins known as “microcystins (MCs)”, which exert their toxicity primarily through the inhibition of serine/threonine protein phosphatases 1 (PP1) and 2A (PP2A). This inhibition disrupts cellular signal transduction pathways and affects numerous cellular processes by preventing the dephosphorylation of proteins. As a result, there is a significant disruption of the cytoskeleton, altered cellular signaling, and, ultimately, cell apoptosis. Additionally, microcystins interfere with cellular antioxidant defense mechanisms, causing oxidative stress by generating reactive oxygen species (ROS). This oxidative stress can lead to damage across various organs and tissues, including the liver, which is particularly susceptible to microcystin toxicity. This chapter provides a comprehensive overview of how physicochemical parameters influence the proliferation of Microcystis sp. and the production of microcystins. It explores the intricate relationship between environmental factors and the enhanced biosynthesis of these toxins, thereby elucidating the conditions that lead to their intensified production.