Emerging microsystems such as portable and implantable medical electronics, wireless micro sensors and next-generation portable multimedia devices demand a dramatic reduction in energy consumption. The ultimate goal is to power these devices using energy harvesting techniques such as vibration-to-electric conversion or through wireless power transmission. A major opportunity to reduce the energy consumption of digital circuits is to scale supply voltages to 0.5V and below. The challenges associated with ultra-low-voltage design will be presented. These include variation-aware design for logic and SRAM circuits, efficient DC-DC converters for ultra-low-voltage structuring to support extreme parallelism.