This chapter explores the background to the need for pharmacovigilance and describes in the main mechanisms by which this is studied in the UK: the Yellow Card Spontaneous Reporting Scheme, and Prescription-Event Monitoring (PEM). It describes two co-existing and complementary pharmacovigilance systems. The chapter also describes statistical methods for detecting signals of adverse drug reactions (ADRs) in a database of spontaneously collected reports. PEM monitors the safety of newly licensed medicines on a national scale and uses a non-interventional cohort design that does not interfere in the prescribing decisions of the practitioners, or specify strict inclusion criteria that occur within randomised controlled trials (RCTs). The HIV ADR reporting scheme is an extension of the Yellow Card Scheme. Reports are made on blue cards. Its aim is to promote knowledge about the safety of drugs used in HIV patients and to encourage reporting. The Yellow Card spontaneous reporting system and PEM provide complementary information on hazards associated with medicines.