Guanosine 3′,5′-cyclic monophosphate (cGMP) is a cyclic nucleotide derived from guanosine triphosphate (GTP). Cyclic GMP is a cellular regulatory agent that acts as a second messenger. Its levels increase in response to a variety of signals (acetylcholine, insulin, oxytocin). cGMP is involved in the regulation of kinases G. cGMP binds to sites on the regulatory units of protein kinase G (PKG) and activates the catalytic units, enabling them to phosphorylate their substrates. cGMP is a common regulator of ion channel conductance, glycogenolysis, and cellular apoptosis. It also relaxes smooth muscle tissues. In blood vessels, relaxation of vascular smooth muscles lead to vasodilation and increased blood flow. cGMP is a secondary messenger in phototransduction in the eye. In the photoreceptors of the mammalian eye, the presence of light activates cGMP phosphodiesterase 5 (PDE5), which degrades cGMP. The sodium ion channels in photoreceptors are cGMP-gated, so degradation of cGMP causes sodium channels to close, which leads to the hyperpolarization of the photoreceptor's plasma membrane and ultimately to visual information being sent to the brain. Mutations in the cGMP phosphodiesterase cause defects in cGMP metabolism leading to retinal disease. Inhibition of cGMP degrading PDE5 by its selective inhibitor sildenafil induced migraine without aura in 10 of 12 migraine patients and in healthy subjects.