Abstract: The harmful algal blooms (HABs) of Microcystis have frequently occurred in the drinking water sources such as Lake Taihu, Chaohu, and Dianchi, posing a severe risk to public health and aquaculture. A series of physical, chemical, and biological measures have been performed for controlling Microcystis blooms in recent years. The secretion of extracellular polymeric substances (EPS) are required for cyanobacterial colonial formation, survival and bloom-forming. Little is known about the biosynthesis pathways of EPS and colonial formation. Previously it has been revealed that multiple putative PEP-CTERM domain-containing proteins are encoded in the genome of Microsytis species and many other cyanobacteria. More recently, we have demonstrated that the PEP-CTERM proteins are required for the floc-formation of Zoogloea resiniphila, a proteobacterium isolated from activated sludge. More interestingly, Microcystis and many other cyanobacteria also encoded a subfamily of PEP-CTERM domain, termed cyano-PEP. It is strongly suggested that such the recently found PEP-CTERM/Cyanoexosortase systems might play a central role in the colonial formation of cyanobacteria. It remains elusive whether the quorum sensing (QS) systems are encoded in cyanobacterial genome and whether the QS is involved in the formation of Microcystis blooms. It is urgent to develop the genetic manipulation in Microcystis and other bloom-forming cyanobacteria for identification of relevant genes and mechanisms underlying colonial formation and for development of Microcystis bloom-controlling techniques.