BACKGROUND: Clinical signs are a core outcome domain for atopic dermatitis (AD) trials. The current lack of standardization of outcome measures in AD trials hampers evidence-based communication. OBJECTIVE: We sought to provide evidence-based recommendations for the measurement of clinical signs in AD trials and to inform the Harmonising Outcome Measures for Atopic Dermatitis Initiative. METHODS: We conducted a systematic review on measurement properties of outcome measurements for clinical signs of AD. We systematically searched MEDLINE and Embase (until October 1, 2012) for validation studies on instruments measuring the clinical signs of AD. Grading of the truth, discrimination, and feasibility of scales; methodological study quality; and recommendations were based on predefined criteria. RESULTS: Sixteen eligible instruments were identified, of which 2 were best validated. The Eczema Area and Severity Index has adequate validity, responsiveness, internal consistency, intraobserver reliability, and intermediate interobserver reliability but unclear interpretability and feasibility. The Severity Scoring of Atopic Dermatitis Index (SCORAD) has adequate validity, responsiveness, interobserver reliability, and interpretability and unclear intraobserver reliability. Only the objective SCORAD (ie, the clinical signs domain of the SCORAD) is internally consistent. The Six Area, Six Sign Atopic Dermatitis Index severity score and Three Item Severity Score fulfill some quality criteria, but the performance in other required measurement properties is unclear. The Patient-oriented Eczema Measure is reliable and responsive but has inadequate content validity to assess clinical signs of AD. The remaining 11 scales have either (almost) not been validated or performed inadequately. CONCLUSIONS: The Eczema Area and Severity Index and SCORAD are the best instruments to assess the clinical signs of AD. The other 14 instruments identified are (currently) not recommended because of unclear or inadequate measurement properties.