Programmable microfluidic platforms (PMPs) are enabling significant advances in the utility of microfluidics for chemical and biochemical analysis. Traditional microfluidic devices are analogous to application-specific devices--a new device is needed to implement each new chemical or biochemical assay. PMPs are analogous to digital electronic processors--all that is needed to implement a new assay is a change in the order of operations conducted by the device. In this review, we introduce PMPs based on normally-closed microvalves. We discuss recent applications of PMPs in diverse fields including genetic analysis, antibody-based biomarker analysis, and chemical analysis in planetary exploration. Prospects, challenges, and future concepts for this emerging technology will also be presented.