This chapter provides a condensed summary and critical analysis of the state-of-the-art knowledge and active research directions on flow boiling in microchannels. The treatment is motivated by high heat flux cooling applications in microelectronics and high-energy physics, where microscale flow boiling is extensively used for reliable cooling. In particular, it is not the objective here to review or describe all the work that has been published on this topic, but instead to present a compact treatment of some typical results and prediction methods, together with an assessment of where we stand today on the most important topics, and what is in the authors’ opinion the most promising way forward in the science of two-phase channel flows. After discussing the macro-to-microscale transition in two-phase flow and heat transfer, this chapter provides a description of two-phase flow observations and flow patterns, void fraction, pressure drop, heat transfer, and critical heat flux with flow boiling in microchannels. This is followed by a detailed description of two flow pattern-based mechanistic models recently developed for slug flow and annular flow. Finally, the chapter includes good practice recommendations for experiments, data reduction, and modeling in microscale two-phase flow boiling.