This Commentary considers the health system and policy challenges of addressing non-communicable diseases (NCDs) in Egypt, Libya, and Tunisia, countries in the process of re-framing state policies and institutions, including in the health sector. Against this backdrop, a neglected issue of the rapidly rising burden of NCDs threatens both health and economic development. Tackling this worrisome rise in NCDs has been impeded by inadequate policies. Weak health systems, little attention to determinants of health, and limited access to affordable health care complicate effective responses to NCDs, especially in a fragile transitional phase. There remains an opportunity to confront the neglected challenge of NCDs by substantially strengthening policies and scaling up comprehensive health systems to more effectively address the causes and treatment of NCDs, including mental health, ultimately to improve population health overall.