Retrospective case-control studies suggest a connection between chronic treatment with fenoterol and other beta-2-agonists and increased mortality from asthma. These studies are extremely difficult to assess from a methodological point of view. They raise important questions, however, and force us to critically reevaluate our present therapeutic approach. In the acute situation, beta-2-agonists might be life-saving, and we must therefore be cautious in readily accepting a causal relationship between beta-2-agonist treatment and death from asthma. Probably, retrospective case-control studies are inadequate to establish a clear-cut association between beta-2-agonist therapy and death from asthma. This will require prospective randomized studies including large asthma populations providing accurate information on both chronic and acute drug treatment, and the end-point is death from asthma.