Future global health security requires a health and care workforce (HCWF) that can respond effectively to health crises as well as to changing health needs with ageing populations, a rise in chronic conditions and growing inequality. COVID-19 has drawn attention to an impending HCWF crisis with a large projected shortfall in numbers against need. Addressing this requires countries to move beyond a focus on numbers of doctors, nurses and midwives to consider what kinds of healthcare workers can deliver the services needed; are more likely to stay in country, in rural and remote areas, and in health sector jobs; and what support they need to deliver high-quality services. In this paper, which draws on a Policy Brief prepared for the World Health Organization (WHO) Fifth Global Forum on Human Resources for Health, we review the global evidence on best practices in organising, training, deploying, and managing the HCWF to highlight areas for strategic investments. These include (1). Increasing HCWF diversity to improve the skill-mix and provide culturally competent care; (2). Introducing multidisciplinary teams in primary care; (3). Transforming health professional education with greater interprofessional education; (4). Re-thinking employment and deployment systems to address HCWF shortages; (5). Improving HCWF retention by supporting healthcare workers and addressing migration through destination country policies that limit draining resources from countries with greatest need. These approaches are departures from current norms and hold substantial potential for building a sustainable and responsive HCWF.