Combinatorial biosynthesis is a new tool in the generation of novel natural products and for the production of rare and expensive natural products. The basic concept is combining metabolic pathways in different organisms on a genetic level. As a consequence heterologous organisms provide precursors from their own primary and secondary metabolism that are metabolised to the desired secondary product due to the expression of foreign genes. In this review we discuss the possibilities and limitations of combining genes from different organisms and the expression of heterologous genes. Major focuses are fundamentals of the genetic work, used expression systems and latest progress in this field. Combinatorial biosynthesis is discussed for important classes of natural products, including alkaloids (vinblastine, vincristine), terpenoids (artemisinin, paclitaxel) and flavonoids. The role and importance of today's used host organisms is critically described, and the latest approaches discussed to give an outlook for future trends and possibilities.