The specific diseases and conditions where it is used include gouty arthritis, skin tophi, kidney stones, idiopathic gout; uric acid lithiasis; acute uric acid nephropathy; neoplastic disease and myeloproliferative disease with high cell turnover rates, in which high urate levels occur either spontaneously, or after cytotoxic therapy; certain enzyme disorders which lead to overproduction of urate, for example: hypoxanthine-guanine phosphoribosyltransferase, including Lesch–Nyhan syndrome; glucose 6-phosphatase including glycogen storage disease; phosphoribosyl pyrophosphate synthetase, phosphoribosyl pyrophosphate amidotransferase; adenine phosphoribosyltransferase.

Allopurinol was also commonly used to treat tumor lysis syndrome in chemotherapeutic treatments, as these regimens can rapidly produce severe acute hyperuricemia;[13] however, it has gradually been replaced by urate oxidase therapy.

Meta-analytic evidence showed that adjunctive allopurinol was superior to placebo for acute mania (both with and without mixed features).

[23] Allopurinol is one of the drugs commonly known to cause Stevens–Johnson syndrome and toxic epidermal necrolysis, two life-threatening dermatological conditions.

[23] More rarely, allopurinol can also result in the depression of bone marrow elements, leading to cytopenias, as well as aplastic anemia.

Increased levels of these ribonucleotides may cause feedback inhibition of amidophosphoribosyl transferase, the first and rate-limiting enzyme of purine biosynthesis.

[28] The HLA-B*5801 allele is a genetic marker for allopurinol-induced severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).

[32] However, the American College of Rheumatology recommends screening for HLA-B*5801 in high-risk populations (e.g. Koreans with stage 3 or worse chronic kidney disease and those of Han Chinese and Thai descent), and prescribing patients who are positive for the allele an alternative drug.

[33] The Clinical Pharmacogenetics Implementation Consortium (CPIC)[34] guidelines state that allopurinol is contraindicated in known carriers of the HLA-B*5801 allele.

[5][37] Allopurinol inhibits the breakdown (catabolism) of the thiopurine drug mercaptopurine, and was later tested by Wayne Rundles in collaboration with Gertrude Elion's lab at Wellcome Research Laboratories to see if it could improve treatment of acute lymphoblastic leukemia by enhancing the action of mercaptopurine.

[5][38] However, no improvement in leukemia response was noted with mercaptopurine-allopurinol co-therapy, so that work turned to other compounds and the team then started testing allopurinol as a potential therapeutic for gout.

Allopurinol is a generic drug sold under a variety of brand names, including Allohexal, Allosig, Milurit, Alloril, Progout, Ürikoliz, Zyloprim, Zyloric, Zyrik, and Aluron.