Non-communicable diseases, including cardiovascular diseases, cancers, respiratory diseases, diabetes, and mental disorders, and injuries have become the major causes of morbidity and mortality in Pakistan. Tobacco use and hypertension are the leading attributable risk factors for deaths due to cardiovascular diseases, cancers, and respiratory diseases. Pakistan has the sixth highest number of people in the world with diabetes; every fourth adult is overweight or obese; cigarettes are cheap; antismoking and road safety laws are poorly enforced; and a mixed public-private health-care system provides suboptimum care. Furthermore, almost three decades of exposure to sociopolitical instability, economic uncertainty, violence, regional conflict, and dislocation have contributed to a high prevalence of mental health disorders. Projection models based on the Global Burden of Disease 2010 data suggest that there will be about 3•87 million premature deaths by 2025 from cardiovascular diseases, cancers, and chronic respiratory diseases in people aged 30-69 years in Pakistan, with serious economic consequences. Modelling of risk factor reductions also indicate that Pakistan could achieve at least a 20% reduction in the number of these deaths by 2025 by targeting of the major risk factors. We call for policy and legislative changes, and health-system interventions to target readily preventable non-communicable diseases in Pakistan.