Polyketides are a fascinating class of natural products with highly diverse, often complex structures combined with a likewise impressive breath of strong and selective biological activities. This chapter discusses the logic of biosynthetic polyketide assembly. It focuses on the introduction of the basic mechanisms and concepts of polyketide core structure assembly using a number of well-studied representative examples, thus allowing to compare the biosynthetic versus chemical synthetic strategies to assemble such beautiful small molecules. Despite the structural diversity of polyketide natural products, there are only few different catalytic domains facilitating a small number of basic reactions common to all types of PKSs that are crucial for product biosynthesis. The structural and functional space covered by bioactive small molecules is further expanded by post-PKS functionalization reactions catalyzed by so-called tailoring enzymes. This includes reorganization of the entire PKS core but also subtle changes by group transfer reactions or oxidative transformations.