The concept of employing photonic crystal fibers for chemical and (photo)-catalytical transformations is presented. These optofluidic microdevices represent a versatile platform where light and fluids can interact for spectroscopic or photoactivation purposes. The use of photonic crystal fibers in chemistry and sensing is reviewed and recent applications as catalytic microreactors are presented. Results on homogeneous catalysis and the immobilization of homogeneous and heterogeneous catalysts in the fiber channels are discussed. The examples demonstrate that combining catalysis and the excellent light guidance of photonic crystal fibers provides unique features for example, for photocatalytic activation and quantitative photospectroscopic reaction analysis.