This book constitutes the refereed proceedings of the 21st International Conference on Case-Based Reasoning Research and Development (ICCBR 2014) held in Cork, Ireland, in September 2014. The 35 revised full papers presented were carefully reviewed and selected from 49 submissions. The presentations cover a wide range of CBR topics of interest both to researchers and practitioners including case retrieval and adaptation, similarity assessment, case base maintenance, knowledge management, recommender systems, multiagent systems, textual CBR, and applications to healthcare and computer games.