NSAIDs (non steroidal anti-inflammatory drugs) are a crucial component for the therapy of pain induced by inflammatory and degenerative joint diseases. Nevertheless their known therapeutic efficacy is contrasted by significant side effects. The recently developed selective COX-2-inhibitors appear to have a better gastrointestinal safety profile, especially relevant to patients with an increased risk for gastrointestinal ulcers and bleeding. However, this effect may similarly be reached by the combination of NSAIDs with proton pump inhibitors. Recent data relate to an elevated myocardial infarction rate in patients using COX-2-inhibitors. This risk may also occur in conventional NSAIDs. Therefore an individual risk calculation is necessary before COX-2-inhibitors or NSAIDs are used. Treatment should be performed with the lowest dosage for the shortest time possible. Combination therapy with salicylic acid seems to abolish the protective effect of COX-2-inhibitors in the GI-tract. Definite risk factors for the treatment with NSAIDs and COX-2-inhibitors have to be defined in further studies providing the best treatment schedule for an individual patient.