There are four major Lewy body disorders with dementia: Parkinson's disease (PD), PD with Alzheimer's disease (AD), cortical Lewy bodies and neuritic plaques, and cortical Lewy bodies and no concomitant AD-type pathology. A variety of pathogenetic processes may underly this panoply of diseases including oxidative stress, excitatory amino acid toxicity, amyloidogenesis, neurofibrillary tangle formation, inflammation, apoptotic cell death, and neurotransmitter deficiency. Treatment strategies include transmitter replacement, neuroprotection, agents to limit AD-type pathology, iron chelation, and anti-inflammatory drugs. Patients with Lewy body disorders exhibit cognitive decline resulting from a variety of disease processes and treatment must address the disease-specific pathogenesis.