Bisphosphonates (e.g., pamidronate, clodronate, alendronate) are pyrophosphate analogs, traditionally used in the treatment of pathologic conditions associated with abnormal bone metabolism, such as osteoporosis, Paget’s disease, and cancer-related bone pain. Recent research shows encouraging results regarding efficacy in often difficult-to-treat chronic pain syndromes, including complex regional pain syndrome and osteoarthritic low back pain. These results and a benign safety profile make bisphosphonate infusion an intriguing modality for physicians to consider for patients suffering from these conditions.