The five muscarinic acetylcholine receptors (mACHRs M1-M5) are an important family of Class A GPCRs widely expressed throughout the central and peripheral nervous systems, where they mediate many of the actions of the neurotransmitter, acetylcholine. Alterations in mAChR levels and activity, particularly with respect to the M4 and M5 mAChR subtypes, have been implicated in the pathophysiology of major neurological and psychiatric diseases, including Alzheimer's disease, Parkinson's disease, mood disorders, schizophrenia and drug addiction. As such, mAChRs have remained important targets for drug discovery, despite the difficulty associated with designing molecules to selectively target the highly conserved orthosteric binding site. While crystal structures of the M1-M4 mAChRs have been determined, there are only a few ligand-bound structures that exist, including no structures of the M5 receptor. This lack of structural information can preclude structure- and/or diversity-based drug discovery efforts, and increasing the number of co-crystal structures of different ligands bound to the same receptor can help in this regard. We will report our recent progress towards determining structures of the M4 and M5 receptors in complex with different ligands.