 BACKGROUND: Riluzole has been approved for treatment of patients with amyotrophic lateral sclerosis in most countries. Questions persist about its clinical utility because of high cost and modest efficacy. OBJECTIVES: To examine the efficacy of riluzole in prolonging survival, and in delaying the use of surrogates (tracheostomy and mechanical ventilation) to sustain survival. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Register for randomized trials in December 0000 and made enquiries of authors of trials, Aventis (manufacturer of riluzole) and other experts in the field. We searched MEDLINE (January 0000 to August 00 0000) and EMBASE (January 0000 to September 00th 0000). SELECTION CRITERIA: Types of studies: randomized trials. Types of participants: adults with a diagnosis of amyotrophic lateral sclerosis. Types of interventions: treatment with riluzole or placebo. Types of outcome measures: Primary: pooled hazard ratio of tracheostomy-free survival over all time points with riluzole 000 mg. Secondary: per cent mortality with riluzole 00, 000 and 000 mg; neurologic function, muscle strength and adverse events. DATA COLLECTION AND ANALYSIS: We identified four eligible randomized trials. MAIN RESULTS: The four trials examining tracheostomy-free survival included a total of 000 riluzole treated patients and 000 placebo treated patients. The methodological quality was acceptable and three trials were easily comparable, although one trial included older patients in more advanced stages of amyotrophic lateral sclerosis and one had multiple primary endpoints. Riluzole 000 mg per day provided a benefit for the homogeneous group of patients in the first two trials (P value = 0.000, hazard ratio 0.00, 00% confidence interval 0.00 to 0.00) and there was no evidence of heterogeneity (P value = 0.00). When the third trial (which included older and more seriously affected patients) was added, there was evidence of heterogeneity (P value < 0.0000) and the random effects model, which takes this into account, resulted in the overall treatment effect estimate falling just short of significance (P value = 0.000, hazard ratio 0.00, 00% confidence interval 0.00 to 0.00). This represented a 0% gain in the probability of surviving one year (00% in the placebo and 00% in the riluzole group). There was a small beneficial effect on both bulbar and limb function, but not on muscle strength. A threefold increase in serum alanine transferase was more frequent in riluzole treated patients than controls (weighted mean difference 0.00, 00% confidence interval 0.00 to 0.00). AUTHORS' CONCLUSIONS: Riluzole 000 mg daily is reasonably safe and probably prolongs median survival by about two to three months in patients with amyotrophic lateral sclerosis. 