Nearly half of known antibiotics act on the ribosome,an important and enduring antibacterial target.Although its size and complexity have always presented special challenges,X-ray crystallography of ribosomes has revolutionized our understanding of this target.I will describe how new insights into ribosome function and the intervention of antibiotics in this process are changing our understanding of antibiotic mechanism and suggesting new sub-targets that have not yet been exploited.Although the ribosome is now amenable to structure based drug design,access to this technology can be limited by the notoriously unreliable process of ribosome crystallization.I describe a program at Pfizer to develop novel ribosome purification technologies and to systematically assess factors that enable crystallization.This has led to robust production of 50S subunit crystals from Deinococcus radiodurans.High quality crystals are consistently generated,and structures can be turned around fast enough to drive an industrial SBDD program.Finally,the impact of crystal structures on a discovery program is described.