The posterior segments of the eye are exquisitely protected from the external environment. This poses unique and fairly challenging hurdles for drug delivery. It is somewhat dogmatic that topical ocular delivery is insufficient to achieve therapeutic drug levels in the posterior segments. However, some drugs are currently challenging this dogma. In this review we investigate the constraints and challenges of drug delivery to the posterior segment. Additionally, we outline several potential absorption pathways that may potentially be exploited to deliver drug to the back of the eye. Data on several compounds that achieve therapeutic posterior segment concentrations after topical dosing is presented. Finally, the issues surrounding systemic delivery to the posterior segment are reviewed.