The use of nanoparticles as carriers for the delivery of therapeutic materials to target tissues has became popular in recent years and has demonstrated great potentials for the treatments of a wide range of diseases. In this review, we summarize the advantages of nanotechnology as a common gene delivery strategy with emphasis on ocular therapy. Particular attention is paid to the CK30-PEG compacted DNA nanoparticles that have been successfully tested in the eye, lung, and brain. These particles resulted in higher transfection efficiency and longer duration of expression than other non-viral vectors without any toxicity or other side effects. They have been safely used clinically and are efficient for a broad range of gene therapy applications. The review also discusses mechanisms of nanoparticle uptake and internalization by cells, obstacles and limitations to the use of this technology, as well as novel methodologies to optimize nanoparticle driven gene expression.