Multimorbidity (two or more coexisting conditions in an individual) is a growing global challenge with substantial effects on individuals, carers and society. Multimorbidity occurs a decade earlier in socioeconomically deprived communities and is associated with premature death, poorer function and quality of life and increased health-care utilization. Mechanisms underlying the development of multimorbidity are complex, interrelated and multilevel, but are related to ageing and underlying biological mechanisms and broader determinants of health such as socioeconomic deprivation. Little is known about prevention of multimorbidity, but focusing on psychosocial and behavioural factors, particularly population level interventions and structural changes, is likely to be beneficial. Most clinical practice guidelines and health-care training and delivery focus on single diseases, leading to care that is sometimes inadequate and potentially harmful. Multimorbidity requires person-centred care, prioritizing what matters most to the individual and the individual’s carers, ensuring care that is effectively coordinated and minimally disruptive, and aligns with the patient’s values. Interventions are likely to be complex and multifaceted. Although an increasing number of studies have examined multimorbidity interventions, there is still limited evidence to support any approach. Greater investment in multimorbidity research and training along with reconfiguration of health care supporting the management of multimorbidity is urgently needed.