Willow bark has a long history of traditional use for musculoskeletal comfort. Several randomized human trials illustrate its actions due to salicin, a source of salicylic acid. Additionally, it helps to maintain healthy prostaglandin metabolism and blood flow. Boswellia serrata has also revealed the potential to provide statistically significant support for joint comfort. AKBA, or 3-acetyl-11-keto-beta-boswellic acid, may be particularly supportive in maintaining healthy 5-lipoxygenase enzyme activity and leukotriene metabolism to maintain tissue comfort. Curcumin maintains healthy cyclooxygenase-2 enzyme activity while supporting healthy prostaglandin, leukotriene and thromboxane metabolism. Devil’s claw promotes both healthy cyclooxygenase-2 and 5-lipoxygenase enzyme activity. A review of 12 human studies indicates that devil’s claw may promote musculoskeletal comfort and function. DL-Phenylalanine supports enkephalin activity.