In the review, we have attempted to show the growing momentum in the area of unconjugated pteridine research. The de novo biosynthetic pathway of tetrahydrobiopterin has been recently clarified. The development of specific assays to measure pteridines in biological fluids has facilitated the acquisition of data on changes in the levels of pteridines during the course of various diseases. Several human inborn errors of its metabolism have been discovered and have become an important resource to elucidate the consequences of tetrahydrobiopterin deficiency. Changes in pteridine metabolism have also been investigated in diseases involving stimulation of cellular mediated immunological processes.