The production of clean diesel by hydrotreating and deep hydrodesulfurization (HDS) has attracted increased attention recently due to the introduction of new environmental legislation regarding fuel specifications. In order to meet the specifications there is a need to modify and improve existing reactors and processes and to introduce more active and selective catalysts. The removal of sterically hindered sulfur-containing molecules is observed to be a key issue for deep HDS. Also the choice of operation conditions and reactor internals play an important role for deep HDS. The present article will focus on key hydrotreating options available to obtain ultra low sulfur diesel levels and some of the theoretical and experimental structure-activity relationships which may aid catalyst developments.