Time span of literature covered: 2010-2018The genome mining of streptomycetes has revealed their great biosynthetic potential to produce novel natural products. One of the most promising exploitation routes of this biosynthetic potential is the refactoring and heterologous expression of corresponding biosynthetic gene clusters in a panel of specifically selected and optimized chassis strains. This article will review selected recent reports on heterologous production of natural products in streptomycetes. In the first part, the importance of heterologous production for drug discovery will be discussed. In the second part, the review will discuss recently developed genetic control elements (such as promoters, ribosome binding sites, terminators) and their application to achieve successful heterologous expression of biosynthetic gene clusters. Finally, the most widely used Streptomyces hosts for heterologous expression of biosynthetic gene clusters will be compared in detail. The article will be of interest to natural product chemists, molecular biologists, pharmacists and all individuals working in the natural products drug discovery field.