Two approaches for incorporating carbon nanotubes into monolithic columns for HPLC are described in this report. They pertain to the investigation of carbon nanotubes either (i) as entities to modulate solute retention on monolithic columns bearing well defined retentive ligands or (ii) as entities that constitute the stationary phase responsible for solute retention and separation. Approach (i) involved the incorporation of carbon nanotubes into octadecyl monolithic columns while approach (ii) concerns the preparation and evaluation of an ideal monolithic support and coating it with carbon nanotubes to yield a real “carbon nanotube stationary phase” for the HPLC separation of a wide range of solutes. First, an octadecyl monolithic column based on the in situ polymerization of octadecyl acrylate and trimethylolpropane trimethacrylate was optimized for use in HPLC separations of small and large solutes (e.g., proteins). To further modulate the retention and separation of proteins, small amounts of carbon nanotubes were incorporated into the octadecyl monolith column. In approach (ii), an inert, relatively polar monolith based on the in situ polymerization of glyceryl monomethacrylate (GMM) and ethylene glycol dimethacrylate (EDMA) proved to be the most suitable support for the preparation of “carbon nanotube stationary phase”. This carbon nanotube “coated” monolith proved useful in the HPLC separation of a wide range of small solutes including enantiomers. In approach (ii), a more homogeneous incorporation of carbon nanotubes into the diol monolithic columns (i.e., GMM/EDMA) was achieved when hydroxyl functionalized carbon nanotubes were incorporated into the GMM/EDMA monolithic support. In addition, high power sonication for a short time enhanced further the homogeneity of the monolith incorporated with nanotubes. In all cases, nonpolar and π interactions were responsible for solute retention on the monolith incorporated carbon nanotubes.