Nitric oxide and cyclic GMP are common and important messengers in cell regulation with more than 150,000 research publications in numerous areas of biology. They participate in blood flow, blood pressure, platelet aggregation and blood clotting, cardiac, gastrointestinal, renal, neuronal and immunologic functions, inflammation, atherosclerosis, wound healing, and stem cell and cancer proliferation to name a few of their effects. The pathways for their formation and biochemical/biological effects have permitted an understanding of the mechanism of action and/or discovery of many important drugs. Defining their biochemical pathways and biological effects have permitted drugs to be developed to treat hypertension, heart attacks, blood clotting, pulmonary hypertension, endothelial dysfunction, bacterial toxin diarrhea, erectile dysfunction, infections, wound healing and cancer. These possible therapeutic applications have further stimulated the research interests in cell signaling pathways. Murad F Nobel Lecture. Bioscience Reports 19, 133-154, 1999. Murad F Shattuck Lecture. New England Journal Med. 355, 2003-2011, 2006.