Pain is one of the most common reasons for seeking medical intervention, and self‐medication with over‐the‐counter medications and/or traditional herbal remedies has become increasingly popular. In this review, original articles on understanding possible herb–drug interactions between traditional herbs and four major pain medications—acetaminophen, aspirin, ibuprofen and naproxen—are compiled and analyzed. In terms of analytical methods, high‐performance liquid chromatography using an isocratic eluent system coupled to biological sample clean‐up is the most common, while a wide variety of detectors have been observed, including a photodiode array, variable wavelength detector, electrochemical detector and tandem mass spectrometer. Both synergistic and anti‐synergistic effects were observed for acetaminophen and aspirin, while only synergistic effects have been found for naproxen. Currently, no interactions have been reported for ibuprofen.