Demands on modern combinatorial chemistry have necessitated massive investment in new synthetic technologies that will allow the production of highly pure drug candidates on short timescales. The advent of microfluidic reactor technologies has recently provided a new tool for the combinatorial chemist, offering the promise of ultra-high-throughput solution-phase chemistries. This review describes why such microscale systems provide unique environments for performing high-efficiency molecular synthesis, details some of the most important recent developments in the field and assesses the true applicability of micro-engineered reactors in high-throughput compound synthesis.