Population studies and World Health Organisation (WHO) statistics indicate that 10-50% of individuals suffer from musculoskeletal disorders. Up to 3% will be classified as disabled due to their bone and joint condition, and the majority will suffer from pain. Almost all will require non-steroidal anti-inflammatory drugs (NSAIDs) and other analgesics for their management. The large majority of this population is elderly and, hence, at greater risk of adverse effects to the NSAIDs. The NSAIDs are a necessary choice in pain management because of the integrated role of the cyclo-oxygenase (COX) pathway in the generation of inflammation and in the biochemical recognition of pain. For over 80 years the management of musculoskeletal pain was hampered by NSAID toxicity problems related to the traditional NSAIDs. In the early 1990s, paracetamol was recommended as the first-choice analgesic for osteoarthritis, but subsequent studies have shown that paracetamol has a significant gastrointestinal (GI) toxicity profile. In addition, it has lower analgesic efficacy than NSAIDs and is, thus, not an effective alternative to NSAIDs in any of the inflammatory arthritides. The identification of cyclo-oxygenase 2 (COX-2) and the subsequent introduction of the COX-2-selective inhibitor NSAID drugs was thought to be a major breakthrough with the expectation of a significant reduction in G/I side-effects. This has not been the case for celecoxib, and indeed for all COX-2-selective inhibitors when given with ASA. The COX-2-selective inhibitors also inhibit renal COX-2 with the potential for problems of fluid retention, oedema, hypertension and congestive heart failure. The major controversy with respect to the COX-2-selective inhibitors as a class has been the increase in myocardial infarction and other cardiovascular events observed in some studies. Thus, the initial expected global benefits of the COX-2-selective inhibitors may be outweighed by their potential for toxicity. Recent studies have shown that the use of a proton-pump inhibitor drug with traditional NSAIDs and with COX-2-selective inhibitors has been shown to significantly reduce GI symptoms and peptic ulceration. Thus, the traditional NSAIDs have been re-established as the preferred choice in the management of arthritis and musculoskeletal disorders.