P(II) signalling proteins constitute a large superfamily of signal perception and transduction proteins, which is represented in all domains of life and whose members play central roles in coordinating nitrogen assimilation. Generally, P(II) proteins act as sensors of the cellular adenylylate energy charge and 2-oxoglutarate level, and in response to these signals, they regulate central nitrogen assimilatory processes at various levels of control (from nutrient transport to gene expression) through protein-protein interactions with P(II) receptor proteins. An examination of the phylogeny of cyanobacteria reveals that specific functions of P(II) signalling evolved in this microbial lineage, which are not found in other prokaryotes. At least one of these functions, regulation of arginine biosynthesis by controlling the key enzyme N-acetyl-L: -glutamate kinase (NAGK), was transmitted by the ancestral cyanobacterium, which gave rise to chloroplasts, into the eukaryotic domain and was conserved during the evolution of planta. We have investigated in some detail the P(II) signalling protein, its signal perception and its interactions with receptors in the unicellular cyanobacteria Synechococcus elongatus PCC 7942 and Synechocystis PCC 6803 and have performed comparative analysis with Arabidopsis thaliana P(II)-NAGK interaction. This chapter will summarize these studies and will describe the emerging picture of a complex network of P(II) protein interactions in the unicellular cyanobacteria.