The remarkable success of two lipid nanoparticle-mRNA vaccines against coronavirus disease (COVID-19) has placed the therapeutic and prophylactic potential of messenger RNA (mRNA) in the spotlight. It has also drawn attention to the indispensable role of lipid nanoparticles in enabling the effects of this nucleic acid. To date, lipid nanoparticles are the most clinically advanced non-viral platforms for mRNA delivery. This is thanks to their favorable safety profile and efficiency in protecting the nucleic acid from degradation and allowing its cellular uptake and cytoplasmic release upon endosomal escape. Moreover, the development of lipid nanoparticle-mRNA therapeutics was already a very active area of research even before the COVID-19 pandemic, which has likely only begun to bear its fruits. In this Review, we first discuss key aspects of the development of lipid nanoparticles as mRNA carriers. We then highlight promising preclinical and clinical studies involving lipid nanoparticle-mRNA formulations against infectious diseases and cancer, and to enable protein replacement or supplementation and genome editing. Finally, we elaborate on the challenges in advancing lipid nanoparticle-mRNA technology to widespread therapeutic use.