The New Zealand Intensive Medicines Monitoring Programme (IMMP) was established in 1977 to enhance monitoring for previously unrecognised adverse drug reactions associated with selected new medicines. This involved establishing cohorts from prescription data and collection of event information: thus New Zealand was a pioneer in the development of the methodology now known as Prescription Event Monitoring (PEM). In the IMMP, PEM cohorts are established using information, supplied by pharmacies, from prescriptions for medicines that have been selected for monitoring. Events are identified subsequently from follow-up questionnaires to prescribing physicians and from other sources, including spontaneous reporting of events. The objective of this review is to illustrate how the IMMP methodology enables identification of signals of previously unrecognised adverse reactions. This is enhanced by high response rates from pharmacists and prescribers in providing prescription and event data respectively. In addition, high quality event reports are obtained from multiple sources including follow-up event returns from prescribers, reports received through the national spontaneous reporting programme, prescription returns and from record linkage to other databases. Collaboration with other national centres and with the WHO Collaborating centre for international drug monitoring in Uppsala, Sweden (WHO-UMC) enables information on cases from their databases to be used in validation of IMMP signals. The NZ IMMP methodology and signals of previously unrecognised adverse drug reactions arising from the IMMP databases are reviewed. Recent signals include amnesia and QTc prolongation with sibutramine; pain activation with sumatriptan; epistaxis with risperidone; psychiatric and visual disturbances with the COX-2 inhibitors celecoxib and rofecoxib and psoriasis with rofecoxib. In addition, other types of investigation are discussed along with the importance of rapid communication to prescribers of new information concerning the risks of medications. The IMMP has features that differ from those of other centres that incorporate PEM methodology. New Zealand is a small country (approximately 4 million) and thus communication is relatively easy. This facilitates good rapport with prescribing doctors. However, mainly because of the small population, several years may be required to achieve a large cohort. Although this has drawbacks in terms of rapid results, it enables a longitudinal approach to prescription data analysis, including aspects of prescribing such as reasons for cessation of therapy and changes in prescribing practise. Although not specifically reviewed in this article, the programme has also made significant contributions in determining the incidence of certain adverse drug reactions and in carrying out in-depth epidemiological investigations relating to the safe use of medicines. Through these activities, the New Zealand IMMP provides an ongoing contribution to safety in the use of medicines.