Objectives: To build a critical appraisal of the available literature to evaluatethe effectiveness of topical calcineurin inhibitors, tacrolimus andpimecrolimus in treatment of atopic dermatitis (AD), in comparison to thecurrent standard therapies: topical corticosteroids (TCs) and emollients.Design: Systematic review and meta-analysis.Review methods:- Data sources: Electronic search of MEDLINE Pubmed along the last 10years (1997-2006) and cross reference search.- Study selection: Randomised control trials of topical tacrolimus orpimecrolimus reporting efficacy outcomes, in comparison to TCs or vehicle(placebo) or both.- Data extraction: Outcomes of interest were the investigator's globalassessment of AD and pruritus severity score (in pimecrolimus studies),physician's global evaluation of response (in tacrolimus studies), andpatient’s global assessment of response (in both). For long term studies, dataabout frequency of flares of AD and steroid free periods were also included.- Validity assessment: followed the standard methodological guidelines forassessment of internal and external validity of the primary studies.Data synthesis: Of 210 articles identified, 19 studies were included, 10 fortacrolimus and 9 for pimecrolimus, involving a total of 7378 patients ofwhom 2771 applied tacrolimus, 1783 applied pimecrolimus, and 2824 werecontrols.Trial reports were of varying quality. Both drugs were significantly moreeffective than a vehicle control. There is very little evidence aboutpimecrolimus compared to TCs. However, two long term trials comparing pimecrolimus to vehicle demonstrated its value in reduction of flaresincidence and its steroid sparing effect after six months.Compared to TCs, both 0.1% and 0.03% tacrolimus ointments were aseffective as moderate potency TCs at three weeks, and more effective than acombined regimen, for 12 weeks, of hydrocortisone butyrate 0.1% (moderateTCs on the trunk) and hydrocortisone acetate 1% (mild TCs on the face).Tacrolimus was also more effective than mild TCs alone.Conclusions: Both topical pimecrolimus and tacrolimus in AD are moreeffective than placebo. Although less effective than topical corticosteroids,pimecrolimus has its value in long term maintenance and steroid sparingeffect in atopic dermatitis (AD), whenever used early enough, at firstappearance of erythema and/or itching. In treatment of moderate to severeAD, topical tacrolimus is as effective as moderately potent topicalcorticosteroids, and more effective than mild preparations. Chronic ADlesions of the face and flexures are the most justified indication for TCIs.