Effectively preventing and managing chronic illness are key goals for health systems worldwide. A growing number of people are living longer with multiple chronic illnesses, accompanied by a high degree of treatment burden and heavy use of health care resources. However, there is a lack of cohort studies on people with multimorbidity, leaving a poor understanding of risk factors that may lead to health problems in the first place or exacerbations thereafter. There is a need to further understand why health problems arise and what predictive factors are amenable to change. Understanding the nature of risk factors into chronic illness as well as risk factors into progressive decline after illness onset can inform both chronic disease prevention and management strategies for not only patients with multimorbidity but all populations at risk.