Anticholinergics, or antimuscarinic drugs, are drugs that competitively inhibit the action of acetylcholine at muscarinic receptors, leading to a blockade of the actions of the parasympathetic nervous system at sites where overactivity can lead to increased symptom burden. Successful blockade of the parasympathetic nervous system ultimately leads to decreased production of secretions in the salivary, bronchial, and gastrointestinal tracts. These effects are often used for several symptoms that originate due to parasympathetic nervous system overactivity, such as the “death rattle” and malignant bowel obstruction. Anticholinergic agents are divided into either tertiary amines or quaternary ammonium compounds, which differ in their ability to cross into the central nervous system. Quaternary compounds do not cross into the central nervous system and have a different adverse effect profile than the tertiary amines. The purpose of this review is to highlight anticholinergic agents, their pharmacology, and an evidence-based assessment of their role in palliative care.