Pain is described as the fifth vital sign, yet its importance is frequently not fully recognised, despite 68 000 000 analgesic prescriptions being dispensed annually. GPs treat pain in the context of a wide spectrum of patient conditions and co-morbidities, recognising potential drug interactions and side-effects. They also factor in the patient’s anxieties, coping strategies, cultural background and previous experiences of pain. It is no wonder that we frequently do not get it right first time. This article discusses the pharmacological action of the major groups of analgesic drugs, considers common pitfalls, and suggests appropriate drug dosing. A titrated multi-modal approach is recommended to target nociceptor pain pathways, and to reduce the side-effects caused by large doses of monotherapy. It discusses the novel use of analgesic agents previously only used for chronic pain. It does not, however, discuss acute-on-chronic pain, drug tolerance, drug addiction or complex pain management.