As we continue to discover new and innovative small molecules and therapeutic compounds, over 80% of those candidates in drug pipeline are challenging to development due to their poor solubility and bioavailability. There are several ocular barriers such as tear film, corneal, conjunctival and blood barriers that cause the bioavailability issues. A nanotechnology-based drug delivery system (NODS) remains the acceptable and eff ective ways for ocular administration of drugs. This article will describe the basic understanding of challenges in ocular drug delivery and the future trends in development of innovative drugs.