Topical drug delivery for sinonasal disorders is influenced by a variety of factors. Macroscopically (or anatomically), the ability of the drug to reach the appropriate region of the paranasal system is paramount. Delivery techniques, surgical state of the sinus cavity, delivery device, and fluid dynamics (volume, pressure, position) have a significant impact on the delivery of topical therapies to the sinus mucosa. Once topical therapeutics actually reach the desired site, factors within the local microenvironment heavily influence local drug delivery. The presence and composition of the mucus blanket, mucociliary clearance, direct mucin-drug binding, and the permeability of pharmaceutical compounds will all impact drug delivery. In addition, the general therapeutic goal of topical management may lie between the potentially competing actions of mechanical lavage and pharmaceutical intervention. Techniques for the mechanical removal of mucus, antigen, and inflammatory products may not be the most efficient approach for pharmaceutical delivery. This article reviews the evolving concepts in local drug therapy, both for the factors that influence anatomic distribution within the sinonasal system and those that affect mucosal absorption.