BACKGROUND: The GRADE-CERQual (Confidence in Evidence from Reviews of Qualitative research) approach has been developed by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) Working Group. The approach has been developed to support the use of findings from qualitative evidence syntheses in decision-making, including guideline development and policy formulation. CERQual includes four components for assessing how much confidence to place in findings from reviews of qualitative research (also referred to as qualitative evidence syntheses): (1) methodological limitations, (2) coherence, (3) adequacy of data and (4) relevance. This paper is part of a series providing guidance on how to apply CERQual and focuses on CERQual's methodological limitations component. METHODS: We developed the methodological limitations component by searching the literature for definitions, gathering feedback from relevant research communities and developing consensus through project group meetings. We tested the CERQual methodological limitations component within several qualitative evidence syntheses before agreeing on the current definition and principles for application. RESULTS: When applying CERQual, we define methodological limitations as the extent to which there are concerns about the design or conduct of the primary studies that contributed evidence to an individual review finding. In this paper, we describe the methodological limitations component and its rationale and offer guidance on how to assess methodological limitations of a review finding as part of the CERQual approach. This guidance outlines the information required to assess methodological limitations component, the steps that need to be taken to assess methodological limitations of data contributing to a review finding and examples of methodological limitation assessments. CONCLUSIONS: This paper provides guidance for review authors and others on undertaking an assessment of methodological limitations in the context of the CERQual approach. More work is needed to determine which criteria critical appraisal tools should include when assessing methodological limitations. We currently recommend that whichever tool is used, review authors provide a transparent description of their assessments of methodological limitations in a review finding. We expect the CERQual approach and its individual components to develop further as our experiences with the practical implementation of the approach increase.