The treatment of pain, in particular, chronic pain, remains a clinical challenge. This is particularly true for pain associated with severe or rare conditions, such as bone cancer pain, vulvodynia, or complex regional pain syndrome. Over the recent years, there is an increasing interest in the potential of bisphosphonates in the treatment of pain, although there are few papers describing antinociceptive and anti-hypersensitizing effects of bisphosphonates in various animal models of pain. There is also increasing evidence for clinical efficacy of bisphosphonates in chronic pain states, although the number of well-controlled studies is still limited. However, the mechanisms underlying the analgesic effects of bisphosphonates are still largely elusive. This review provides an overview of preclinical and clinical studies of bisphosphonates in pain and discusses various pharmacological mechanisms that have been postulated to explain their analgesic effects. LINKED ARTICLES: This article is part of a themed issue on The molecular pharmacology of bone and cancer-related bone diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.9/issuetoc.