Rechallenge is defined as the readministration of a medication suspected of being a possible cause of an adverse reaction and which has been discontinued as result. It may be unintentional when the appearance of a reaction was initially not attributed to the medication. A rechallenge may be intentional when a prescriber decides that the benefit of rechallenge will outweigh its risk. When considering intentional rechallenge, one should take into account the benefit/risk balance of the suspected causative medication, and the benefit/risk balance of the best available alternative treatment or no treatment. Clinical knowledge is essential in benefit/risk assessment but there is currently no suitable tool to guide the decision on rechallenge. This article aims to propose points to consider in the creation of reaction-specific algorithms for risk assessment and management in the case of drug rechallenge.