This article reviews the objectives which must be considered in producing optimal formulations for topical ophthalmic use. The effects of preservatives, vehicles, and adjunct agents are described. Anatomical considerations which impact bioavailability of the drug at the desired target site are discussed in detail. Model systems that can aid in determining the best formulations for preclinical and clinical testing are also reviewed. The long term objective of this review is the development of formulations for optimal efficacy and safety, considering all the requirements of the patient.