Frameworks for the teaching and assessment of 21st-century skills commonly recognise the importance of learning and skill development in the interpersonal domain. They also usually acknowledge the challenge of reliably and validly assessing students in this domain. In the field of medical education and in selecting students for medical courses, the concept of empathy has become central to representing the particular interpersonal understandings and skills expected of students and practising doctors. Attempts to assess these attributes during medical training are just as challenging as in school contexts. This presentation draws on several years’ experience of working with medical educators to consider how empathy has been conceptualised, taught and assessed by educators. This analysis explores three common assessment approaches: self-report, performance examinations, and longitudinal observation and judgement in the clinical context. Each approach addresses important aspects of empathy and interpersonal skills. Each also has its limitations, although the self-report approach has emerged as the more widely known and used in medical education. Much still remains to be understood about making meaningful and valid use of observational judgements in the assessment of empathy, and, by extension, the interpersonal domain. In the meantime, useful guidance for teachers assessing interpersonal skills in the classroom may be found in alternative learning frameworks currently used in professional education that precede the 21st-century skills movement.