Cyanobacterium Synechocystis sp. PCC 6803, a popular model organism for researches in photosynthesis and biofuel production, contains plant-like photosynthetic machineries which significantly contribute to global carbon fixation. There are 12 eukaryotic-type Ser/Thr kinases (SpkA-L) and 49 His kinases (Hik1-49) of two-component systems in the genome of Synechocystis sp. PCC 6803. They are the key regulators in sensing and transmitting stimuli including light- and glucose-mediate signal transduction. Proteomic studies were able to identify all the kinases. The majority of kinases no matter whether they have a predicted transmembrane domain were identified in the membrane fractions. Six Ser/Thr kinases (SpkA-D, F and G) and ten His kinases (Hik4, 12, 14, 21, 26-27, 29, 36, 43, and 46) were identified to have one or more of the three types of post-translational modifications: phosphorylation, acetylation, and thiol oxidation. Interestingly, SpkG has the phosphorylatable threonine residue that was aligned with the phosphorylated threonine residue in the activation loop of human CDK7, demonstrating conserved phosphorylation between cyanobacterial and human kinases. Transcriptomics and proteomics revealed differential expression of the kinases in heterotrophic and photoheterotrophic compared with photoautotrophic conditions, indicating their roles in regulating the growth modes of cyanobacteria. In summary, this review focuses on the discussions on post-transcriptional modifications, transcriptomic, and proteomic studies of Ser/Thr and His kinases. This together with our published review in 2019 present a complete story of an overview of sequences, domain architectures, and biochemical and physiological functions of cyanobacterial kinases with adequate details in the context of high throughput systems. We also emphasize the importance of discovering upstream molecules and substrates to understand the exact functions of the kinases in vivo. As an attempt, a model is proposed in which Hik31, His33, Sll1334, and IcfG are hypothesized to be critical for switching between autotrophic and heterotrophic modes based on the results from the phenotypes of the gene knockout strains combined with their post-translational modifications, and gene expression profiles.