The article reviews the impact of particle size and polydispersity index (PDI) on the clinical applications of lipidic nanocarrier systems. Lipid-based drug delivery systems, such as liposomes, nanoliposomes, and solid lipid nanoparticles, are widely used to enhance the bioavailability of poorly soluble drugs. The physical attributes of these nanocarriers, including average particle size and PDI, significantly influence their safety, stability, efficacy, and in vitro and in vivo behavior. Controlling and validating these parameters are crucial for effective clinical applications. The review highlights the significance of size and PDI in the design, formulation, and development of nanosystems for pharmaceutical, nutraceutical, and other applications. It also discusses the advantages and limitations of various analytical techniques used to characterize lipidic nanocarrier formulations, such as microscopy, light scattering, and flow cytometry. The article emphasizes the importance of maintaining a constant and narrow size distribution in nanocarrier formulations to achieve optimal clinical outcomes and stability.The article reviews the impact of particle size and polydispersity index (PDI) on the clinical applications of lipidic nanocarrier systems. Lipid-based drug delivery systems, such as liposomes, nanoliposomes, and solid lipid nanoparticles, are widely used to enhance the bioavailability of poorly soluble drugs. The physical attributes of these nanocarriers, including average particle size and PDI, significantly influence their safety, stability, efficacy, and in vitro and in vivo behavior. Controlling and validating these parameters are crucial for effective clinical applications. The review highlights the significance of size and PDI in the design, formulation, and development of nanosystems for pharmaceutical, nutraceutical, and other applications. It also discusses the advantages and limitations of various analytical techniques used to characterize lipidic nanocarrier formulations, such as microscopy, light scattering, and flow cytometry. The article emphasizes the importance of maintaining a constant and narrow size distribution in nanocarrier formulations to achieve optimal clinical outcomes and stability.