Applications of microsystems (microreactors) in continuous-flow chemistry have expanded rapidly over the past two decades, with numerous reports of higher conversions and yields compared to conventional batch benchtop equipment. Synthesis applications are enhanced by chemical information gained from integrating microreactor components with sensors, actuators, and automated fluid handling. Moreover, miniaturized systems allow experiments on well-defined samples at conditions not easily accessed by conventional means, such as reactions at high pressure and temperatures. The wealth of synthesis information that could potentially be acquired through use of microreactors integrated with physical sensors and analytical chemistry techniques for online reaction monitoring has not yet been well explored. The increased efficiency resulting from use of continuous-flow microreactor platforms to automate reaction screening and optimization encourages a shift from current batchwise chemical reaction development to this new approach. We review advances in this new area and provide application examples of online monitoring and automation.