Dimethyl sulfoxide (DMSO) is a highly versatile aprotic organic solvent widely used in pharmaceutical R&D. The twenty-first century has seen a surge of uses of DMSO in formulations, at the same time as the biologics revolution hits a higher gear with nucleic acid vaccines and therapeutics joining protein biologics in the armamentarium of pharmaceutical products. DMSO’s appeal stems from its versatility: it can dissolve both polar and nonpolar compounds, is completely water miscible, and easily penetrates biological membranes. In drug delivery, DMSO has played roles as a cosolvent, penetration enhancer, and cryoprotectant. The relevance of DMSO is growing with the rise of RNA therapeutics, including messenger RNA (mRNA) and lipid nanoparticle (LNP) delivery systems, where stability of delicate biomolecules like mRNA is of paramount importance. mRNA-based products (notably the COVID-19 mRNA vaccines) rely on LNP carrier particles to protect the mRNA and deliver it into cells. Ensuring these mRNA-LNP formulations remain stable during manufacturing, storage, and delivery is a critical and ongoing challenge. This chapter provides an overview of DMSO’s role in this context—how DMSO can contribute to mRNA therapeutic formulation, stabilizes LNPs, and preserves nucleic acids more generally—along with mechanistic insights and supporting experimental data. As this review is in part forward-looking, it is intended for an audience interested in drug formulation and delivery innovations for practical product development in the future, where the unique properties of DMSO may play impactful roles.