Nitric oxide (NO) synthesis is controlled by Ca(2+)/calmodulin (CaM) binding with and kinase-dependent phosphorylation of constitutive NO synthases, which catalyze the formation of NO and L-citrulline from L-arginine. NO operates as a mediator of important cell signaling pathways, such as cGMP signaling cascade. Another mechanism by which NO exerts biological effects is mediated via post-translational modification of redox-sensitive cysteine thiols of proteins. The Ca(2+)/CaM-dependent protein kinases (CaM kinases) such as CaM kinase I, CaM kinase II, and CaM kinase IV, are a family of protein kinases which requires binding of Ca(2+)/CaM to and subsequent phosphorylation of the enzymes to initiate its activation process. We report other regulation mechanisms of CaM kinases, such as S-glutathionylation of CaM kinase I at Cys(179) and S-nitrosylation of CaM kinase II at Cys(6/30). Such unique post-translational modification of CaMKs by NO shed light on a new area of mutual regulation of NO- and CaM kinases-signals. Based on the novel direct regulation of these kinases, we propose that CaM kinases/NO signaling would be good targets for understanding how they can participate in neuronal physiology and disease.