Non-communicable diseases (NCDs), principally heart disease, stroke, cancer, diabetes, and chronic respiratory diseases, are a global crisis and require a global response. Despite the threat to human development, and the availability of affordable, cost-effective, and feasible interventions, most countries, development agencies, and foundations neglect the crisis. The UN High-Level Meeting (UN HLM) on NCDs in September, 2011, is an opportunity to stimulate a coordinated global response to NCDs that is commensurate with their health and economic burdens. To achieve the promise of the UN HLM, several questions must be addressed. In this report, we present the realities of the situation by answering four questions: is there really a global crisis of NCDs; how is NCD a development issue; are affordable and cost-effective interventions available; and do we really need high-level leadership and accountability? Action against NCDs will support other global health and development priorities. A successful outcome of the UN HLM depends on the heads of states and governments attending the meeting, and endorsing and implementing the commitments to action. Long-term success requires inspired and committed national and international leadership.