Despite 20 years of debate, several US Food and Drug Administration (FDA) hearings, black-box warnings, and many descriptive articles and metaanalyses, controversy regarding the safety of long-acting beta-agonist (LABA) treatment in asthma patients continues. This has resulted in a recent call for another large and definitive safety study. This commentary focuses first on data provided in the metaanalysis recently undertaken by the FDA of safety outcomes among 60,954 individuals in 110 LABA trials, and second on the sample size that would be required for a new definitive study of LABA safety in the presence of mandatory treatment with an inhaled corticosteroid (ICS). A critical stratified analysis in the FDA report involving 15,192 individuals indicates that a LABA used with mandatory ICS therapy was not associated with an increased risk of asthma-related mortality, intubations, or exacerbations (risk difference [RD], 0.25 per 1,000 individuals; 95% confidence interval [CI], -1.69 to 2.18). Using the same stratified data to calculate the sample size required to prove or disprove an association between the use of LABA with mandatory ICS therapy and adverse outcomes, assuming the RD is exactly 0.25, and ignoring the 95% CI, which includes 0.0 or even a negative risk, such a study is both logistically and scientifically impossible. A new study is not practicable, nor is one needed in the light of current analyses of existing data. It is time to learn from the past, to rigorously avoid LABA monotherapy in asthma, and to use a LABA (when indicated) always in mandatory combination with appropriate doses of an ICS.