There has been an awareness of nerve poisons from ancient times. At the dawn of the twentieth century, the actions and mechanisms of these poisons were uncovered by modern physiological and biochemical experimentation. However, the era of selective neurotoxins began with the pioneering studies of R. Levi-Montalcini through her studies of the neurotrophin "nerve growth factor" (NGF), a protein promoting growth and development of sensory and sympathetic noradrenergic nerves. An antibody to NGF, namely, anti-NGF - developed in the 1950s in a collaboration with S. Cohen - was shown to produce an "immunosympathectomy" and virtual lifelong sympathetic denervation. These Nobel Laureates thus developed and characterized the first identifiable selective neurotoxin. Other selective neurotoxins were soon discovered, and the compendium of selective neurotoxins continues to grow, so that today there are numerous selective neurotoxins, with the potential to destroy or produce dysfunction of a variety of phenotypic nerves. Selective neurotoxins are of value because of their ability to selectively destroy or disable a common group of nerves possessing (1) a particular neural transporter, (2) a unique set of enzymes or vesicular transporter, (3) a specific type of receptor or (4) membranous protein, or (5) other uniqueness. The era of selective neurotoxins has developed to such an extent that the very definition of a "selective" neurotoxin has warped. For example, (1) N-methyl-D- aspartate receptor (NMDA-R) antagonists, considered to be neuroprotectants by virtue of their prevention of excitotoxicity from glutamate receptor agonists, actually lead to the demise of populations of neurons with NMDA receptors, when administered during ontogenetic development. The mere lack of natural excitation of this nerve population, consequent to NMDA-R block, sends a message that these nerves are redundant - and an apoptotic cascade is set in motion to eliminate these nerves. (2) The rodenticide rotenone, a global cytotoxin that acts mainly to inhibit complex I in the respiratory transport chain, is now used in low dose over a period of weeks to months to produce relatively selective destruction of substantia nigra dopaminergic nerves and promote alpha-synuclein deposition in brain to thus model Parkinson's disease. Similarly, (3) glial toxins, affecting oligodendrocytes or other satellite cells, can lead to the damage or dysfunction of identifiable groups of neurons. Consequently, these toxins might also be considered as "selective neurotoxins," despite the fact that the targeted cell is nonneuronal. Likewise, (4) the dopamine D2-receptor agonist quinpirole, administered daily for a week or more, leads to development of D2-receptor supersensitivity - exaggerated responses to the D2-receptor agonist, an effect persisting lifelong. Thus, neuroprotectants can become "selective" neurotoxins; nonspecific cytotoxins can become classified as "selective" neurotoxins; and receptor agonists, under defined dosing conditions, can supersensitize and thus be classified as "selective" neurotoxins. More examples will be uncovered as the area of selective neurotoxins expands. The description and characterization of selective neurotoxins, with unmasking of their mechanisms of action, have led to a level of understanding of neuronal activity and reactivity that could not be understood by conventional physiological observations. This chapter will be useful as an introduction to the scope of the field of selective neurotoxins and provide insight for in-depth analysis in later chapters with full descriptions of selective neurotoxins.