Optimizing absorption can present unique demands in many animal studies because where dose-response linearity and high tissue exposure levels are required, doses may be greater than when administered for therapeutic effect. At the same time, investigative molecular constructs designed to enhance potency and specificity can have features that militate against efficient absorption. Pre-treatment or formulation to optimize absorption may be warranted. This article reviews various physicochemical approaches employed for absorption enhancement. Strategies based on capitalizing or neutralizing physiological processes are also discussed, as there is much current interest in exploiting novel non-invasive routes to deliver medicinal agents.