A central role in the immune escape of tumors has been attributed to the kynurenine pathway of tryptophan metabolism, leading to the depletion of tryptophan and the production of different bioactive metabolites. The first and rate-limiting step in this pathway is catalyzed by the phylogenetically unrelated enzymes indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO), which have both been shown to be expressed in different cancers. Intense efforts in academia and in pharmaceutical companies to develop novel inhibitor scaffolds yielded a few compounds currently undergoing clinical trials. Here, we review the most significant compounds in the field and discuss potential issues in the development of kynurenine pathway inhibitors for cancer therapy.