Although a multitude of halogenated compounds are naturally produced, interest in biodegradation of these often toxic compounds has mainly been driven by anthropogenic contamination of soils and aquifers with huge amounts of chlorinated solvents (tetra- and trichloroethene (PCE, TCE), chlorinated ethanes (1,2-DCA, 1,1,1-TCA, and benzenes (1,2-DCB, 1,2,4-TCB)), pesticides (DTT, HCH), flame retardants (PCBs), and others. Many of these chlorinated compounds have intentionally been designed to be resistant to oxidative attack and some are indeed not biodegraded under aerobic conditions. Reductive dechlorination observed under anaerobic conditions led to the hypothesis that chlorinated compounds could be used as terminal electron acceptor in a process nowadays called organohalide respiration (OHR). Isolation and characterization of different organohalide-respiring bacteria (OHRB) in the nineties and the first decade of the 21st century revealed a phylogenetically rather heterogeneous group of bacteria with also contrasting physiologies. Whereas some OHRB are quite versatile, able to use different carbon and energy sources as well as many electron acceptors, such as Desulfitobacterium and Sulfurospirillum spp., others, such as Dehalobacter and Dehalococcoides spp., are obligate OHRB. The latter have, in addition to the already rather surprising feature of being obligate OHRB, a mixotrophic metabolism, a physiological trait that has so far been observed for some sulfur-oxidizing chemolithotrophs and some phototrophs. The purification and characterization of reductive dehalogenases has shown that also on the biochemical level completely new features are involved in this most interesting microbial process with a new class of corrinoid-containing enzymes. Genome analysis of OHRB has furthermore revealed that quite many OHRB have multiple copies of rdhA genes and even rdh operons. However, even though studied now since about twenty years, many aspects of the physiology and biochemistry of OHRB are rather poorly understood. Examples are the topology and composition of the OHR chain, the direct electron donor of reductive dehalogenases, the reaction mechanism of the reductive dechlorination itself, the structure of the corrinoid cofactor and the iron-sulfur centers, and the way the corrinoid cofactor is retained in the reactive site of the reductive dehalogenase. This presentation will summarize the knowns and unknowns of the physiology and biochemistry of OHR and hopefully motivate some young scientists to go after the yet unsolved elementary questions of this anaerobic respiration.