The gum resin from Boswellia serrata (Indian frankincense) has a long history of various medicinal applications and has been appreciated for millennia. Recently, the pharmacological properties and clinical effectiveness of Boswellia serrata have been studied systematically. In particular, B. serrata has been used traditionally against inflammatory diseases. Its main pharmacologically active ingredients are β‐boswellic acids with anti‐inflammatory properties. Among the members of β‐boswellic acid family, 3‐O‐acetyl‐11‐keto‐β‐boswellic acid (AKBA) has been demonstrated as the most active ingredient with anti‐5‐lipooxygenase activity, which is mainly responsible for Boswellia serrata's anti‐inflammatory properties. This chapter describes molecular insight of anti‐inflammatory properties of an AKBA enriched extract of B. serrata (5‐LOXIN) and its clinical efficacy in management of osteoarthritis. A series of in vitro and in vivo experiments, including a GeneChip Microarray study, reveal that 5‐LOXIN modulates several key pro‐inflammatory cytokines/chemokines. A double blind, placebo controlled clinical study conducted on subjects with knee osteoarthritis (OA) demonstrates that oral supplementation of 5‐LOXIN significantly helps in relieving the clinical symptoms of OA and also decreases cartilage destruction by reducing matrix metalloproteinase‐3 (MMP‐3) production in synovial membrane of OA subjects. Together, a battery of safety studies and clinical studies demonstrate that oral supplementation of this AKBA enriched extract of B serrate gum resin (5‐LOXIN) is safe and tolerable for clinical applications. Furthermore, a proprietary composition (Aflapin) has been developed recently, which contains B. serrata extract with at least 30% AKBA and B. serrata non‐volatile oil. In vitro and in vivo experiments suggest that this advanced composition significantly enhances the anti‐inflammatory efficacies by improving the bioavailability of AKBA. In addition, randomized double blinded placebo controlled clinical study has demonstrated that Aflapin provides a prompt and significant improvement in pain relief, physical ability and quality of life in OA subjects.