This chapter deals with the biosynthesis and breakdown of purine and pyrimidine nucleotides. In de novo synthesis of purine nucleotides, the purine ring formed from variety of precursors is assembled on ribose-5-phosphate. Purine nucleotides can also be synthesized by a salvage pathway in which a preformed base reacts directly with phosphoribosylpyrophosphate. In the synthesis of pyrimidine nucleotide the pyrimidine ring is assembled first and then link to ribose-5-phosphate in contrast with sequence in the de novo synthesis of purine nucleotides. Humans catabolize purines to uric acid. Gout, a disease that affects joints and leads to arthritis is associated with hyperuricemia. The Lesch-Nyhan syndrome, a genetic disease is caused by the absence of hypoxanthine-guanine phosphoribosyltransferase (HGPRTase), an enzyme essential for synthesis of purine nucleotides by the salvage pathway. Since pyrimidine catabolites are water soluble their over production does not result in clinical abnormalities. Deficiency of adenosine deaminase (ADA), an enzyme involved in catabolism of purine nucleotides, is associated with severe combined immunodeficiency (SCID). Orotic aciduria can result from a defective enzyme in pyrimidine synthesis.