Nitric oxide (NO) has opened a new and vigorous field of biological and clinical experimentation as evidenced presently by about one hundred original publications every week. Being a biological signal under physiological conditions, NO may be > to pathologically affected tissues. Major insights into the biology and pathology of this unorthodox biomolecule have come from the histochemical analysis of NO synthase (NOS) and its molecular isoforms that are responsible for the formation of NO. Immunocytochemistry as well as NADPH-diaphorase histochemistry are most widely used to visualize NOS in various tissues. There are several constraints regarding specificity and sensitivity of the techniques used and, therefore, apparent discrepancies in the literature concerning the cellular and subcellular distribution of NOS and its isoforms. Despite such inconsistencies there is a wealth of data that has an important impact on further investigation of NO-mediated processes underlying a vast number of NO-mediated physiological and pathological mechanisms.