Early blight (EB), caused by fungus Alternaria solani Sorauer, is a destructive disease of tomato (Lycopersicon esculentum Mill.) in the U.S. and elsewhere. Sources of genetic resistance have been identified within tomato related wild species, in particular green-fruited L. hirsutum Humb. and Bonpl. and red-fruited L. pimpinellifolium (Jusl.) Miller. Resistance was previously reported to be horizontal and quantitative, and transmitted as a dominant, additive, or recessive trait, depending on the cross. Furthermore, EB resistance does not follow the gene-for-gene model of host-pathogen interaction. We have used traditional protocols of plant genetics and breeding and contemporary molecular-marker technology to better understand the genetic basis of EB resistance and to develop tomatoes with improved resistance. Traditional backcross breeding has resulted in development of germplasm with improved resistance, however, linkage drag has been a major obstacle, in particular when using L. hirsutum as the gene source. Several filial and backcross populations were developed from interspecific crosses between L. esculentum and either L. hirsutum or L. pimpinellifolium and used for QTL mapping. In each population, about 7 QTLs were identified for EB resistance. In populations derived from each interspecific cross, approximately half of the QTLs were stable across generations and environments. Across interspecific populations, some QTLs were consistent suggesting the authenticity of these QTLs for use in EB resistance breeding. However, many QTLs were species-specific, suggesting that the L. hirsutum and L. pimpinellifolium accessions harbored different EB resistant genes. This provides an opportunity to pyramid resistance QTLs from the two species using marker-assisted selection (MAS) and to develop tomatoes with strong EB resistance. Further inspection of the results led to the identification and selection of several QTLs with stable and independent effects for use in marker-assisted breeding. However, to facilitate 'clean' transfer and pyramiding of these QTLs, near-isogenic lines (NILs) containing individual QTLs in a L. esculentum background should be developed. In the present study, also several resistance-gene-analogs (RGAs) and candidate disease-resistance/ defense-response genes were identified co-localizing with QTLs, suggesting their potential evolutionary relationship with EB resistance.