Polypharmacy is a phenomenon of modern health care that can offer benefits in terms of patient outcomes. Known risks associated with so-called inappropriate polypharmacy can be reduced through good medicine management and appropriate use of clinical guidelines. However, we now see a growing literature highlighting additional risks to individual well-being and social functioning not recognised within these existing frameworks – the burden of polypharmacy and a problem of overprescribing. We need a new approach to defining and understanding inappropriate polypharmacy from a person-centred perspective. This paper discusses practice-based work exploring the impact of introducing generalist needs assessment for elderly patients with multiple chronic morbidities. The work suggests that generalist care offers something ‘different’ to current chronic disease management models, but highlights the need for formal evaluation to determine whether it is ‘better’. We call for new collaborative research between clinical and academic partners to address the question as to whether generalist care offers solutions to the problems of the burden of polypharmacy.