Root rot diseases remain a major global threat to the productivity of agricultural crops. They are usually caused by more than one type of pathogen and are thus often referred to as a root rot complex. Fungal and oomycete species are the predominant participants in the complex, while bacteria and viruses are also known to cause root rot. Incorporating genetic resistance in cultivated crops is considered as the most efficient and sustainable solution to counter root rot; however, resistance is often quantitative in nature. Several genetics studies in various crops have identified quantitative trait loci associated with resistance. With access to whole genome sequences, the identity of the genes within the reported loci is becoming available. Several of the identified genes have been implicated in pathogen response. However, it is becoming apparent that at the molecular level, each pathogen engages a unique set of proteins to either infest the host successfully or be defeated or contained in doing so. In this review, a comprehensive summary of the genes and potential mechanisms underlying resistance or susceptibility against the most investigated root rots of important agricultural crops is presented.