Inhaled corticosteroids are the mainstay of treatment for persistent asthma because of their proven efficacy, which is better than any other class of antiasthma therapy. Concerns about unwanted systemic effects with long-term use has, however, limited their use. Efforts have been made to develop inhaled corticosteroids with less systemic activity for a given clinical effect, thereby improving their therapeutic index. Many different study designs and outcome variables have been used to compare different inhaled corticosteroids. Differences in pharmacologic properties between drugs are most easily and accurately measured and quantified by measures of systemic effects. However, these differences should always be related to differences in clinical effects. It is difficult to draw firm conclusions with respect to the therapeutic index of different inhaled corticosteroids because no direct placebo-controlled, dose-response comparisons of clinical effects have been made. Despite this caveat, the available studies suggest that microgram for microgram, when delivered by a pressurized metered-dose inhaler (pMDI), fluticasone propionate (FP) is more effective than beclomethasone dipropionate (BDP), triamcinolone acetonide (TAA), or budesonide; however, the efficacy of budesonide delivered by Turbuhaler is equipotent to that of FP delivered by pMDI or Diskhaler and more effective than that of BDP. When comparative safety is considered, budesonide or TAA delivered by pMDI have less systemic activity than FP delivered by pMDI, whereas BDP and FP delivered by pMDI appear to be equivalent. Also, budesonide delivered by Turbuhaler has less systemic activity than FP delivered by Diskhaler.