Pharmacological ocular therapy is one of the great challenges in pharmaceutical technology, particularly for drugs with poor aqueous solubility, as they must overcome the anatomical and physiological barriers of the eye. Drug nanocrystals (NCs) are pure drug particles in the nanometer range that present a large surface area, providing high apparent saturation solubility, enhanced dissolution rates, and improved adhesive properties. These advantages lead to improved drug corneal penetration, prolonged retention in ocular tissues, and higher bioavailability with reduced toxicity and patient discomfort compared to conventional eye drops. In turn, NCs are versatile systems, as they can be incorporated into secondary drug delivery systems, such as in situ gelling systems or microneedles. Whether for treating inflammation, infections, or glaucoma, NCs have shown higher therapeutic effects than conventional treatments. Furthermore, NCs have also proven to be safe, well tolerated, and less toxic than available formulations. This technology has been demonstrated to be simple, cost-effective, and scalable. Several formulations are available as NCs or nanosuspensions (NSs), including those for ocular applications. In this chapter, we discuss the specific challenges of pharmacological ocular therapy, highlighting the advantages of NCs for ocular drug delivery. Furthermore, we review the latest developments in nanocrystal (NC) formulations for ocular applications, including both laboratory-scale preclinical studies and approved ocular formulations.