For several thousand years (~4000) Boswellia serrata and Curcuma longa have been used in Aryuvedic medicine for treatment of various illnesses, including asthma, peptic ulcers, and rheumatoid arthritis, all of which are mediated through pathways associated with inflammation and pain. Although the in vivo pharmacology of both these natural ingredients is difficult to study because of poor bioavailability, in vitro data suggest that both influence gene expression mediated through nuclear factor kappa B (NF-κB). Therefore, the activity of pathways associated with inflammation (including NF-κB and lipoxygenase- and cyclooxygenase-mediated reduction in leukotrienes/prostaglandins) and those involved in matrix degradation and apoptosis are reduced, resulting in a reduction in pain. Additive activity of boswellic acids and curcumin was observed in preclinical models and synergism was suggested in clinical trials for the management of osteoarthritis (OA) pain. Overall, studies of these natural ingredients, alone or in combination, revealed that these extracts relieved pain from OA and other inflammatory conditions. This may present an opportunity to improve patient care by offering alternatives for patients and physicians, and potentially reducing nonsteroidal anti-inflammatory or other pharmacologic agent use. Additional research is needed on the effects of curcumin on the microbiome and the influence of intestinal metabolism on the activity of curcuminoids to further enhance formulations to ensure sufficient anti-inflammatory and antinociceptive activity. This narrative review includes evidence from in vitro and preclinical studies, and clinical trials that have evaluated the mechanism of action, pharmacokinetics, efficacy, and safety of curcumin and boswellic acids individually and in combination for the management of OA pain.