Rheumatoid arthritis (RA) is a chronic inflammatory joint disorder in which people suffer from joint as well as neurobiological disorder. These patients take multiple drugs which opens the chances of drug interaction. Therefore this book deals with the in-vitro and in-vivo interaction studies of leflunomide (a leading DMARD to treat RA) with NSAIDs, essential & trace elements. For in-vitro studies, methods were developed & validated (via ICH guide lines)on UV-spectrophotometer and HPLC which were then applied for drug interaction study. Leflunomide-metals complexes were also synthesized and characterized by IR, H1-NMR and CHN. In-vivo studies were also conducted on chronic (adjuvant induced) and acute (carrageenan induced) arthritic model. Studies highlighted that NSAIDs and metals interact significantly with leflunomideboth in-vitro & in-vivo. In order to study RA associated neurobiological disorder, effect of these drugs were also studies on rat’s brain indolamines level. These results showed that these drugs also affect brain indoleamines level in rats.