Little clinically relevant, evidence-based data about the effect of motility modifiers on the GI tract of cattle are currently available. Additionally, some of the published results seem to be contradictory. Three main facts explain this apparent discrepancy: (1) Results may not be transferred from one species to another, because presence, concentration, location, distribution, and function of specific receptors may differ significantly among species. (2) The lack of a significant effect on smooth muscle preparations in vitro does not necessarily exclude a certain drug's motility-modifying property on affected animals in vivo. Certain drugs bind to receptors outside the myenteric plexus. Others, such as lidocaine and adrenergic-, dopaminergic-, and opioid-antagonists increase only GI motility, if inhibitory reflexes or a hyperactive state of the inhibitory sympathetic nervous system preexists. (3) Effects of motility modifiers as found in healthy experimental animals in vivo may not be similar to those found in spontaneously diseased animals. Accurate and reliable data on the effect of modifiers of GI motility of cattle will be obtained only from double-blinded, evidence-based, in vivo studies on spontaneously affected animals. Because well-documented results from such studies are extremely rare, intensive research in this field is warranted in the future.