When operating microsystems in harsh environments, many conventionally used techniques are limiting. Further, depending on if the demands arise from the environment or the conditions inside the system, different approaches have to be used. This thesis deals with the challenges encountered when microsystems are used at high pressures and high temperatures. For microsystems operating at harsh conditions, many parameters will vary extensively with both temperature and pressure, and to maintain control, these variations needs to be well understood. Covered within this thesis is the to-date strongest membrane micropump, demonstrated to pump against back-pressures up to 13 MPa, and a gas-tight high pressure valve that manages pressures beyond 20 MPa. With the ability to manipulate fluids at high pressures in microsystems at elevated temperatures, opportunities are created to use green solvents like supercritical fluids like CO2. To allow for a reliable and predictable operation in systems using more than one fluid, the behavior of the multiphase flow needs to be controlled. Therefore, the effect of varying temperature and pressure, as well as flow conditions were investigated for multiphase flows of CO2 and H2O around and above the critical point of CO2. Also, the influence of channel surface and geometry was investigated. Although supercritical CO2 only requires moderate temperatures, other supercritical fluids or reactions require much higher temperatures. The study how increasing temperature affects a system, a high-temperature testbed inside an electron microscope was created. One of the challenges for high-temperature systems is the interface towards room temperature components. To circumvent the need of wires, high temperature wireless systems were studied together with a wireless pressure sensing system operating at temperatures up to 1,000 °C for pressures up to 0.3 MPa. To further extend the capabilities of microsystems and combine high temperatures and high pressures, it is necessary to consider that the requirements differs fundamentally. Therefore, combining high pressures and high temperatures in microsystems results in great challenges, which requires trade-offs and compromises. Here, steel and HTCC based microsystems may prove interesting alternatives for future high performance microsystems.