Background: Despite their huge epidemiological impact, primary headaches, trigeminal neuralgia and other chronic pain conditions still receive suboptimal medical approach, even in developed countries. The limited efficacy of current pain-killers and prophylactic treatments stands among the main reasons for this phenomenon. Botulinum neurotoxin (BoNT) represents a well-established and licensed treatment for chronic migraine, but also an emerging treatment for other types of primary headache, trigeminal neuralgia, neuropathic pain, and an increasing number of pain conditions. Methods: We searched and critically reviewed evidence for the efficacy of BoNT for the treatment of chronic pain. Results: Meta-analyses and randomized controlled trials (RCTs) suggest that BoNT potentially represents a multi-purpose drug for the treatment of pain in several disorders due to a favorable safety profile and a long-lasting relief after a single injection. Conclusions: BoNT is an emerging treatment in different pain conditions. Future RCTs should explore the use of BoNT injection therapy combined with systemic drugs and/or physical therapies as new pain treatment strategies.