Nanocrystals and nanosuspensions have become realistic approaches to overcome the formulation challenges of poorly water-soluble drugs. They also represent a less-known but versatile platform for multiple therapeutic applications. They can be integrated into a broad spectrum of drug delivery systems including tablets, hydrogels, microneedles, microparticles, or even functionalized liposomes. The recent progresses, challenges, and opportunities in this field are gathered originally together with an informative case study concerning an itraconazole nanosuspension-in-hydrogel formulation. The translational aspects, historical and current clinical perspectives are also critically reviewed here to shed light on the incoming generation of nanocrystal formulations.