Theophylline is a bronchodilator that also has an anti-inflammatory effect. In Japan, methylxanthines, including theophylline and aminophylline (theophylline ethylenediamine), have been used widely in the treatment of asthma. In some asthma management guidelines, although methylxanthines are recommend for the treatment of asthma, they are not preferred primarily because of potential serious adverse effects in case of overdose. The present review examines the efficacy and adverse effects of sustained-release theophylline and injectable methylxanthines in the treatment of chronic asthma and acute exacerbation of asthma by evaluating reports of published clinical trials and a prospective survey on the occurrence of serious adverse drug reactions to these agents. A prospective survey on the safety of methylxanthines was administered to adult patients (15−64 years of age), mainly with asthma, in medical centers by physicians certified as specialists by the Japanese Society of Allergology. Review of published clinical trials has shown that methylxanthines are effective in controlling asthma. In the prospective study, in the case of sustained-release theophylline, 3921subjects reported by 66 medical centers and meeting the criteria for inclusion in the survey were selected for analysis. In the case of intravenous methylxanthines, 682 subjects reported by 55 medical centers conforming and meeting the criteria for inclusion in the survey were selected for analysis. None of these subjects exhibited serious adverse drug reaction with sustained-release theophylline or intravenous methylxanthines. In conclusion, methylxanthines are effective for the treatment of asthma and are safe as long as the dose administered accords with the protocols recommended by asthma management guidelines.