Poorly soluble drug molecules often have low bioavailability issues and absorption problems in the clinical setting. As the number of poorly soluble drugs increases from discovery, developing technologies to enhance their solubility, while also controlling their release is one of the many challenges facing the pharmaceutical industry today. Liquid crystalline systems, nanoparticulate or macro-matrix, self-assemble in the presence of an aqueous environment and can provide a solubility enhancement, while also controlling the drug release rate. This review examines the fundamentals of liquid crystalline systems through the representative literature, concluding with examples of clinical trial developments. The review focus is on the potential of utilizing liquid crystalline systems for poorly soluble drugs, in the areas of oral delivery and IV/subcutaneous, followed by water soluble molecules. Key considerations in utilizing liquid crystalline systems advantages while also discussing potential areas of key research that may be needed will be highlighted.