Nucleic Acid (NA) based therapeutics are poised to disrupt modern medicine and augment traditional pharmaceutics in a meaningful way. However, a key challenge to advancing NA therapies into the clinical setting and on to the market is the safe and effective delivery to the target tissue and cell. Lipid Nanoparticles (LNP) have been extensively investigated and are currently the most advanced vector for the delivery of NA drugs, as evidenced by the approval of Onpattro for treatment of Amyloidosis in the US and EU in 2018. This article provides a comprehensive review of the state-of-the-art for LNP technology. We discuss key advances in the design and development of LNP, leading to a broad range of therapeutic applications. Finally, the current status of this technology in clinical trials and its future prospects are discussed.