Lateral epicondylitis can be chronic and difficult to manage with conservative measures such as physical therapy and corticosteroid injection. We attempted to determine the efficacy of botulinum toxin for the treatment of chronic lateral epicondylitis. We searched PubMed, MEDLINE, CINAHL, Google Scholar, EMBASE, PEDro, and ISI web of Science databases from inception until November 2009. Studies were included if they used any formulation of botulinum toxin A for treatment of chronic lateral epicondylitis and reported at least 1 pain outcome. One author extracted the relevant data using a standardized data extraction sheet and a second author checked the data. We performed a meta-analysis by computing effect sizes for each study separately for pain and grip strength at 3 months after injection. Impact of bias was assessed independently by 2 authors. The search found 10 studies relevant to the question. Four of these were randomized controlled trials that could be pooled in a meta-analysis. Results showed a moderate effect for pain favoring botulinum toxin (effect size -0.5, 95% CI -0.9, -0.1, I(2) = 56%) at 3 months and a no effect for grip strength. Qualitative analysis of the studies that could not be pooled also showed improvement in pain, but was limited by potential bias. Present literature provides support for use of botulinum toxin A injections into the forearm extensor muscles (60 units) for treatment of chronic treatment-resistant lateral epicondylitis. It is minimally invasive and can be performed in an outpatient setting.