Proteins of the Polycomb group (PcG) and of the trithorax group (trxG) are involved in the regulation of key developmental genes, such as homeotic genes. PcG proteins maintain silent states of gene expression, while the trxG of genes counteracts silencing with a chromatin opening function. These factors form multimeric complexes that act on their target chromatin by regulating post-translational modifications of histones as well as ATP-dependent remodelling of nucleosome positions. In Drosophila, PcG and trxG complexes are recruited to specific DNA elements named as PcG and trxG response elements (PREs and TREs, respectively). Once recruited, these complexes seem to be able to establish silent or open chromatin states that can be inherited through multiple cell divisions even after decay of the primary silencing or activating signal. In recent years, many components of both groups of factors have been characterized, and the molecular mechanisms underlying their recruitment as well as their mechanism of action on their target genes have been partly elucidated. This chapter summarizes our current knowledge on these aspects and outlines crucial open questions in the field.