Drug interactions are often the result of complex biochemical, physical, and kinetic factors and may not often be easily predicted or even recognized. Although this article has attempted to point out the more common mechanisms and results of drug interactions, the few interactions that have been documented in small animals are undoubtedly only the tip of the iceberg. For the safety of patients and for the highest quality of veterinary care, it is essential that the practitioner become thoroughly familiar with the actions and interactions of drugs used in his or her practice and realize the possible consequences of multiple drug therapies before adding another drug to a therapeutic regimen. From a therapeutics standpoint, the temptation to polypharmacy is great, but the adage "an ounce of prevention is worth a pound of cure" is especially appropriate when discussing drug therapy. The rational decision to use as few drugs as possible in any given situation is the route to safe and successful drug therapy.