Among the most critical parameters for any drug candidate are tolerability, dose, solubility and permeability. For controlled release formulations, gastrointestinal transit is an added hurdle. While we might assume that intestinal transit is independent of the drug candidate, the relative importance of gastrointestinal transit time (GITT) depends directly on the other parameters. For example, a formulation of a drug with low solubility (LS) and/or low permeability (LP) characteristics might provide the required systemic concentrations when administered with food, but not if administered on an empty stomach. In the LS case, the drug may require the solubilizing effects of increased fluid and bile salts that accompany the meal. Likewise, a controlled release formulation of a drug with a region of preferred absorption may empty from the fasted stomach and move beyond the region before drug release is complete. Companion animals (e.g. cats and dogs) differ from humans and each other with respect to GITT, food effects, eating habit influences, breed and size variability, gastric pH, intestinal enzymes, GI permeability and absorption regions. This review examines how the anatomy and physiology of companion animals relates to the performance of orally administered immediate and controlled release formulations. Examples are presented of techniques used to predict the dose and acceptable solubility of drug candidates, and the performance of formulations in companion animals.