Nanocrystals, which are pure drug particles sized between 10 and 1000 nm, offer a promising approach for improving the solubility, dissolution rate, and bioavailability of poorly water-soluble drugs. Due to their high surface energy, nanocrystals tend to be unstable and prone to agglomeration, making stabilizers crucial for maintaining their physical stability and controlling particle growth. This chapter thoroughly reviews stabilizer selection, a vital aspect of nanocrystal formulation. Stabilizers are broadly categorized into polymeric, ionic, and nonionic types, with their functional performance significantly influenced by physicochemical parameters such as concentration, molecular weight, hydrophilic–lipophilic balance (HLB), drug solubility in the dispersion medium, surface free energy compatibility, and pH. Specific stabilizers like poloxamers, vitamin E TPGS, hydroxypropyl methylcellulose (HPMC), Soluplus®, and cyclodextrins have been extensively investigated for their unique roles in improving drug delivery by enhancing solubility, stability, and bioavailability of poorly water-soluble drugs. These stabilizers not only prevent particle aggregation and Ostwald ripening but also modulate interactions with biological membranes, potentially enhancing permeability and cellular uptake. Understanding the interplay between stabilizer properties and formulation parameters is critical for optimizing nanocrystal performance in targeted and sustained drug delivery systems.