SDHIs form a highly attractive group of fungicides regarding their history of use, chemical innovations and spectrum of targeted diseases. The mode of action of SDHIs is the inhibition of succinate dehydrogenase in the respiration chain. Along with the broadening of their disease control palette, the structural complexity of the SDHIs has been increased. Current SDHIs share common chemical features, suggesting a similar binding to the target as demonstrated by three-dimensional alignment and computational docking experiments. Different target site mutations (TSM) have been found in field isolates of various fungal species. The acquired SDHI resistance by TSM is highly complex. Some species like Pyrenophora teres came up with more than 10 different TSM in the SDHI subunits conferring SDHI resistance, while others have so far shown up only with a small number of TSM, e.g. Phakopsora pachyrhizi or Sclerotinia sclerotiorum. TSM have been found in gene regions highly conserved over various species, but also in variable regions even on an intraspecific level. Modelling studies indicated that some of the target site mutations conferring resistance to SDHIs have a direct impact on the binding behavior of SDHIs, whereas others influence SDHI binding by long-range structural rearrangement in the transmembrane region of complex II. A diverse and complex picture has also seen regarding the effects of TSM on the sensitivity towards various SDHIs in various pathogens. Some TSM cause a sensitivity reduction to all currently commercialized SDHIs to a more or less extent, but there are also TSM where no complete cross resistance has been found. This led to intensive discussions on SDHI cross resistance and on appropriate resistance management strategies.