Diseases of the posterior segment of the eye account for most cases of irreversible blindness worldwide. Drug delivery to this closed compartment remains a challenge because of the internal and external blood retinal barriers that selectively control drug penetration into the retina. Direct intraocular (intravitreal) delivery is currently used to achieve high drug concentration in the vitreous and the retina but is usually associated with several side effects. Alternatively topical, periocular, and systemic routes of administration can be used but are associated with low bioavailability and specific side effects. Therefore, intraocular sustained drug delivery systems are being designed to overcome these limitations. Polymeric nanoparticles loaded with therapeutic compounds are under investigation to provide new tools of administration to the eye. The first part of this paper will briefly review the barriers to ocular delivery of drugs and the advantages of using polymeric nanoparticle carriers as drug delivery systems. In the second part, the results in terms of preparation and characterization of polymeric nanoparticles loaded with nucleic acids, the study of the transretinal pathway of intravitreally injected nanoparticles and the assessment of their ability to efficiently deliver plasmids and oligonucleotides will be discussed.