The analysis of bioactive compounds in raw bioactive materials by liquid chromatography can prove to be a very difficult task and usually require extended times to adequately separate all components from such complex matrices. Currently there is a great interest in the development of new technology to improve chromatographic performance and reduce the necessary time to achieve the separation between components. Liquid chromatography has seen great improvements in the last decades, especially in stationary phase technology. New stationary phase technologies include sub2 µm particles, partially porous and porous monolithic polymers. These new packing materials are taking the chromatographic performance of separations to a much higher level. Liquid chromatography systems are also seen improvements in term of pressure limits, precision, reproducibility and overall quality of the results. The use of these advanced systems and materials allied to the adoption of carefully planned strategies under optimized conditions can produce excellent chromatographic results with speeds that were thought to be impossible a few years ago. In this context, this chapter discusses current technology available that can be explored to reduce analysis time of bioactive compounds in natural products. It also discusses the influence of most important operational parameters (column In Instrumental Methods for the Analysis and Identification of Bioactive Molecules; Jayprakasha, et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2014.temperature, mobile phase composition and flow rate/ linear velocity in the chromatographic system and how these variables can be adjusted in order to produce the greatest potential for performing separations.