Histone deacetylases (HDACs) are essential catalytic components of the transcription silencing machinery and they play important roles in the programming of multicellular development. HDACs are present within multisubunit protein complexes, other components of which govern HDAC target gene specificity by controlling interactions with sequence-specific DNA-binding proteins. Here, I review the different developmental roles of the Sin3, NuRD, CoREST and NCoR/SMRT Class I HDAC complexes. With their distinct subunit composition, these versatile molecular devices function in many different settings, to promote axis specification and tissue patterning, to maintain stem cell pluripotency, facilitate self-renewal, guide lineage commitment and drive cell differentiation.