Pharmacogenetics tests are being used increasingly to prevent rare and potentially life-threatening adverse drug reactions. For many tests, however, cost-effectiveness is hard to demonstrate and, with the exception of a few cases, widespread implementation remains a distant prospect. Many orphan drugs for rare diseases are also not cost-effective but are nonetheless normally reimbursed. In this article, we argue that the health technology assessment of pharmacogenetics tests aimed to prevent rare but severe adverse drug reactions should be on a level playing field with orphan drugs. This is supported by a number of arguments, concerning the severity, rarity and iatrogenic nature of adverse drug reactions, the distribution of benefits and costs, and the preference placed on prevention over treatment.