Health systems in low- and middle-income countries were designed to provide episodic care for acute conditions. However, the burden of disease has shifted to be overwhelmingly dominated by chronic conditions and illnesses that require health systems to function in an integrated manner across a spectrum of disease stages from prevention to palliation. Low- and middle-income countries are also aiming to ensure health care access for all through universal health coverage. This article proposes a framework of effective universal health coverage intended to meet the challenge of chronic illnesses. It outlines strategies to strengthen health systems through a “diagonal approach.” We argue that the core challenge to health systems is chronicity of illness that requires ongoing and long-term health care. The example of breast cancer within the broader context of health system reform in Mexico is presented to illustrate effective universal health coverage along the chronic disease continuum and across health systems functions. The article concludes with recommendations to strengthen health systems in order to achieve effective universal health coverage.