As the second-generation architecture of microfluidics-based biochips, digital microfluidics provides a flexible, scalable, and high-defect-tolerant system architecture. It enables programmability such that general-purpose biochemical analyses can be carried out in a manner similar to traditional benchtop protocols. As more bioassays are executed concurrently on digital microfluidics platforms, system integration and design complexity are expected to increase dramatically. This article provides an overview of several key issues in the modeling, simulation, synthesis, testing, and runtime reconfiguration of digital microfluidics, and presents an integrated, top-down CAD and test methodology. This methodology is expected to facilitate the integration of digital microfluidics with microelectronic components in next-generation SoCs.