High speed and/or high efficiency separations can be realized using small particles (~ 1 µm) in liquid chromatography (LC). However, due to the large pressure drop caused by small particles, conventional LC pumping systems cannot satisfy the pressure requirements needed to drive the mobile phase through the column. Use of ultrahigh pressure, elevated temperature, or both can overcome these pressure limitations and allow the use of very small particles for high speed and/or high efficiency separations. In this dissertation, the use of ultrahigh pressures with and without elevated temperatures in capillary LC is described. Very fast separations of various samples on silica-based stationary phases were achieved using optimized equipment and conditions. Great reduction in separation time, while maintaining high efficiency, is the most significant result of this work. Mechanically, chemically and thermally stable new packing materials were required for this research. Polybutadiene encapsulated nonporous zirconia particles, which are chemically and thermally more stable than silica, were evaluated for fast separations of pharmaceuticals and herbicides at temperatures and pressures as high as 100 °C and 30 kpsi, respectively. Safety is a concern when extremely high pressures are used in LC. Column rupture and system component failure can lead to the creation of high speed liquid jets and capillary projectiles. The use of a plexiglass shroud to cover the initial section of the installed capillary column can eliminate any safety-related concerns about these liquid jets or capillary projectiles. An ultrahigh pressure sample injector, with small dwell volume is critical for sample injection and gradient operation at high pressures. A novel injection assembly, composed of six small needle valves, withstood pressures as high as 30 kpsi. A new capillary connector was designed to hold the capillary by “two-point” holding forces under high pressures. With this new injector and capillary connector, gradient elution was easily achieved for the high resolution separation of a protein tryptic digest.