Tan spot, caused by Pyrenophora tritici-repentis (Ptr), is a major foliar disease on wheat. The pathosystem involves three pairs of necrotrophic effector (NE) and host sensitivity (S) gene interactions, namely Ptr ToxA-Tsn1, Ptr ToxB-Tsc2 and Ptr ToxC-Tsc1. Additionally, genetic factors conferring race-nonspecific resistance have been identified. The objectives of this study were to map tan spot resistance QTL and investigate the role of NE-S interactions in disease in durum using association and bi-parental mapping. Evaluation of a worldwide collection of durum accessions allowed identifying highly resistant nineteen lines to multiple Ptr races. Association mapping revealed genomic regions on chromosomes 1A, 2B and 3B significantly associated with resistance to tan spot, which likely correspond to Tsc1, Tsc2 and racenonspecific resistance. Using a bi-parental population derived from Ben and PI 41025, we found that ToxA-Tsn1 interaction plays no significant role in disease, instead a major race-nonspecific QTL on chromosome 5A was identified.