In this editorial discussion we reflect on the issues addressed by, and arising from, the papers in this special issue on Single-Case Experimental Design (SCED) study methodology. We identify areas of consensus and disagreement regarding the conduct and analysis of SCED studies. Despite the long history of application of SCEDs in studies of interventions in clinical and educational settings, the field is still developing. There is an emerging consensus on methodological quality criteria for many aspects of SCEDs, but disagreement on what are the most appropriate methods of SCED data analysis. Our aim is to stimulate this ongoing debate and highlight issues requiring further attention from applied researchers and methodologists. In addition we offer tentative criteria to support decision-making in relation to the selection of analytical techniques in SCED studies. Finally, we stress that large-scale interdisciplinary collaborations, such as the current Special Issue, are necessary if SCEDs are going to play a significant role in the development of the evidence base for clinical practice.