It is believed that 40–60% of Americans use complementary and alternative medicine to treat a variety of medical conditions. Of these Americans, 30% cite pain as the primary condition being treated. The clinical use of nutritional modulators as a treatment of pain has been widely studied. Pain states such as myalgias from statin use, rheumatoid arthritis, menstrual pain, and osteoarthritis, just to name a few, have been investigated. Strong evidence supports the use of probiotics, omega-3 fatty acids, magnesium, glucosamine/chondroitin, and vitamin D in a variety of pain states. Other modulators including turmeric, devil’s claw, methylsulfonylmethane (MSM), Boswellia, white willow bark, and green tea have contradictory or minimal evidence to support their use for pain relief. Despite the medical evidence or lack thereof, passionate consumers continue to utilize these modulators as supplements or alternatives to traditional pharmacotherapy.