Nitric oxide (NO) is a key mammalian signaling molecule that affects numerous physiological processes. Mammals possess three isoforms of nitric oxide synthase (NOS): endothelial (eNOS), neuronal (nNOS), and inducible (iNOS). These isoforms differ in their tissue distribution, cellular location, regulation, and NO output. NO synthesized by eNOS and nNOS acts in a paracrine fashion, whereby NO generated in one cell acts upon an adjacent cell by binding to and activating soluble guanylyl cyclase (sGC). Activation of sGC by NO leads to a several hundredfold enhancement of cyclic guanidine monophosphate (cGMP) synthesis. Notable outcomes of elevated cGMP levels are neurotransmission and smooth muscle relaxation. iNOS is capable of synthesizing much higher steady-state levels of NO, and the toxicity of NO is harnessed as part of the innate immune response. In recent years, it has become increasingly clear that NO targets proteins other than sGC. S-nitrosation is an example of nonclassical NO signaling, defined as sGC/cGMP-independent, and has garnered attention with regard to the regulation of NOS activity both in vitro and in vivo. The purpose of this review is to cover what is currently known about the S-nitrosation of NOS isoforms.