High-fidelity simulation tools that couple fluid flow, heat transfer and chemistry of PCR microreactors have been applied to different microreactor designs. The tools are coupled to a controller software for thermal control of the virtual reactors. The numerical tools can be used for comprehensive simulations of PCR microreactors for assessment of DNA amplification, control and uniformity of temperature and can be used to optimize reactor geometry, heater/cooler placement and to generate controller schedules. Results for different PCR reactor designs are presented and demonstrate the capability of such tools and their utility during the design phase.