© 2015 © 2015 Informa Healthcare. The simultaneous presence of multiple conditions in one patient (multi-morbidity) is a key challenge facing healthcare systems globally. It potentially threatens the coordination, continuity and safety of care. In this paper, we report the results of a scoping review examining the impact of multi-morbidity on the quality of healthcare. We used its results as a basis for a discussion of the challenges that research in this area is currently facing. In addition, we discuss its implications for health policy and clinical practice. The review identified 37 studies focussing on multi-morbidity but using conceptually different approaches. Studies focusing on comorbidity (i.e. the index disease approach) suggested that quality may be enhanced in the presence of synergistic conditions, and impaired by antagonistic or neutral conditions. Studies on multi-morbidity (i.e. multiplicity of problems) and morbidity burden (i.e. the total severity of conditions) suggested that increasing number of conditions and severity may be associated with better quality of healthcare when measured by process or intermediate outcome indicators, but with worse quality when patient-centred measures are used. However, issues related to the conceptualization and measurement of multi-morbidity (inconsistent across studies) and of healthcare quality (restricted to evaluations for each separate condition without incorporating considerations about multi-morbidity itself and its implications for management) compromised the generalizability of these observations. Until these issues are addressed and robust evidence becomes available, clinicians should apply minimally invasive and patient-centred medicine when delivering care for clinically complex patients. Health systems should focus on enhancing primary care centred coordination and continuity of care.