Microfluidics-based biochips enable the precise control of nanoliter volumes of biochemical samples and reagents. They combine electronics with biology and integrate various bioassay operations, such as sample preparation, analysis, separation, and detection. Compared to conventional laboratory procedures, which are cumbersome and expensive, miniaturized biochips offer the advantages of higher sensitivity, lower cost, system integration, and less likelihood of human error. Because of these advantages, microfluidic biochips are being increasingly used for DNA sequencing, point-of-care clinical diagnostics, and immunoassays. This chapter describes three mainstream microfluidic technology platforms: (1) flow-based microfluidics, (2) digital microfluidics, and (3) microelectrode-dot-array biochips. The chapter presents recent advances in computer-aided design tools for simulation, synthesis, and chip optimization. These tools target modeling and simulation, scheduling, module placement, and droplet routing. With the help of these tools, biochip users can concentrate on the development of nanoscale bioassays, leaving details of chip optimization and implementation to software tools.