The exothermic reactions with fast intrinsic kinetics when carried out in conventional reactors are often limited by heat transfer. This results in the formation of hot spots, which affects product distribution of complex reactions and may lead to reactor runaway. Microstructured reactors (MSR) have been successfully used for this type of reaction, gaining increased temperature control and enhanced safety. Although different MSR concepts have been applied to various processes, the general design criteria are still poorly discussed in the literature. In this review, temperature management in conventional single injection MSR is described. The important issues, such as reactor safety and stability, along with the role of mixing, are discussed in detail. Subsequently, the multi-injection reactor concept is introduced and a simplified model developed to investigate the temperature profile is presented. Finally, the benefits and critical issues in the design of multi-injection MSR are highlighted.