This study is focused to review some of the most exciting discoveries regarding how plant pathogenic fungi use the histidine-kinase phosphorelay to coordinate distinct events of their life; such is the case of osmotic adjustment, cell cycle regulation, virulence, cell wall assembly, sensing and response to environmental changes and finally, how pathogenic fungi acquires fungicide resistance against dicarboxiimide and phenylpyrroles. Particular emphasis is given to the group III of histidine-kinases, also known as the NIK1 class, because experimental evidence through gene sequencing, mutant isolation and gene knock outs is showing that in plant pathogenic fungi, the HK group III is the main responsible for the acquisition of resistance to some important fungicides. These finding support and suggests that fundamental changes should be considered in the strategies that are currently being used to control important plant pathogens like Botrytis cinerea, Cochliobolus heterostrophus, Alternaria brassicicola and Magnaporthe grisea.