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Background: The paper combines the analytical and instrumental perspectives on communities of practice (CoPs) to reflect on potential challenges that may arise in the process of interprofessional and inter-organisational joint working within the Collaborations for Leaderships in Applied Health Research and Care (CLAHRCs)-partnerships between the universities and National Health Service (NHS) Trusts aimed at conducting applied health research and translating its findings into day-to-day clinical practice. Discussion: The paper discusses seminal theoretical literature on CoPs as well as previous empirical research on the role of these communities in healthcare collaboration, which is organised around the following three themes: knowledge sharing within and across CoPs, CoP formation and manageability, and identity building in CoPs. It argues that the multiprofessional and multi-agency nature of the CLAHRCs operating in the traditionally demarcated organisational landscape of the NHS may present formidable obstacles to knowledge sharing between various professional groupings, formation of a shared 'collaborative' identity, and the development of new communities within the CLAHRCs. To cross multiple boundaries between various professional and organisational communities and hence enable the flow of knowledge, the CLAHRCs will have to create an effective system of 'bridges' involving knowledge brokers, boundary objects, and cross-disciplinary interactions as well as address a number of issues related to professional and organisational identification. Summary: The CoP approach can complement traditional 'stage-of-change' theories used in the field of implementation research and provide a basis for designing theory-informed interventions and evaluations. It can help to illuminate multiple boundaries that exist between professional and organisational groups within the CLAHRCs and suggest ways of crossing those boundaries to enable knowledge transfer and organisational learning. Achieving the aims of the CLAHRCs and producing a sustainable change in the ways applied health research is conducted and implemented may be influenced by how effectively these organisations can navigate through the multiple CoPs involved and promote the development of new multiprofessional and multi-organisational communities united by shared practice and a shared sense of belonging-an assumption that needs to be explored by further empirical research. [ABSTRACT FROM AUTHOR]