This review deals with the potency of monoclonal antibodies (MAbs) to haptens in immunoassays. Specificity and affinity of MAbs to haptens are the major determinants to be considered. Despite careful attention to both these requirements, polyspecific effects can occur leading to unforeseen cross-reactivity with compounds more or less related to the native hapten. This polyspecificity may be circumvented by the development of a large number of MAbs, as has been demonstrated for MAbs to cyclosporine. Affinity of MAbs to hapten is often lower than than of corresponding polyclonal antibodies (PAbs). Selection of appropriate specificity and affinity may depend on the analytical aim of the immunoassay. Pharmacokinetics requires MAbs with high specificity and affinity, while for therapeutic drug monitoring, toxicology or drug abuse detection a wider specificity and a lower affinity may be needed. If the strategy for selecting MAbs is carefully complied with, MAbs exhibit real advantages over classical PAbs to haptens because large amounts of worldwide standardized reagents can be prepared.