Food quality has a profound impact on various life history traits, including life span, development time and resistance to infections. In the current study, we used isofemale lines originated from African and European populations that cover a broad range of performances regarding different life history traits. These isofemale lines showed very different survival rates even on standard medium, which is indicative of a significant impact of the genotype on their overall performance. It was hypothesised that different nutritive yeast species influence life history traits. Thus, we used two different yeast species that are usually associated with Drosophila and that may function as major food sources under natural conditions. Adding either yeast species Pichia toletana or Metschnikowia pulcherrima as a food source, increased survival rate and decreased development time; P. toletana was more effective than M. pulcherrima. This difference was also reflected in a behavioural choice assay showing that P. toletana was more attractive than M. pulcherrima. Pichia toletana had not only positive effects on the different life history traits under control conditions, but it also increased the resistance to infection with the pathogenic bacterium Pseudomonas stutzeri. Confrontation with either yeast species induced expression of the antimicrobial peptide gene drosomycin. The expression pattern of this antimicrobial peptide was similar to what is observed after stress-induced activation of the immune system rather than that observed after conventional infection with a pathogen. The results presented in this study support the hypothesis that different nutritive yeast species affect Drosophila survival rate, decrease development time and increase resistance to infection. This study provides evidence that the fitness of Drosophila critically depends on the fly's genotype as well as the nutritive yeasts.