Nanocrystals (NCs) have emerged as a highly effective approach to enhance the oral delivery of poorly water-soluble drugs, which represent a significant portion of new and existing therapeutics. Poor aqueous solubility limits drug dissolution and absorption, posing major challenges for oral bioavailability and clinical efficacy. By reducing drug particle size to the nanometre scale, NCs improve dissolution rate and saturation solubility, leading to more consistent pharmacokinetics and enhanced bioavailability. These improvements allow for lower doses, reduced dosing frequency, and increased patient compliance, key benefits for oral therapies. The field of oral NCs remains a focus of active research and commercial development, driven by the urgent need to address solubility issues affecting numerous drugs. Despite challenges in manufacturing scale-up and stability, advances in formulation science continue to expand the clinical applications of NCs. Overall, the NC technology provides a clinically validated and versatile platform to overcome solubility and absorption limitations, supporting the development of safer and more effective oral drug formulations. This chapter covers the oral administration route, its challenges, and how NCs overcome solubility and absorption issues, reviewing recent studies and marketed NC-based oral formulations.