Pioneers and leading researchers explain the theory and techniques of using targeted toxins experimentally. The highly successful use of the 192 IgG-saporin and ME20.4-saporin immunotoxins to lesion the cholinergic basal forebrain in order to model the behavior, anatomy, physiology, and pharmacology of Alzheimer’s disease in animals is treated in detail to give a potential user the knowledge to comfortably use the techniques involved. The uses of important new lesioning agents such as anti-DBH-saporin immunotoxin to make remarkably selective lesions of catecholaminergic neurons, hypocretin-saporin that can produce narcoleptic animals, and other saporin conjugates, such as neuropeptide-saporin conjugates for pain research and cholera toxin B chain-saporin to produce a model of CNS demyelination are explained by experts in the field.