The genetic basis of natural variation in disease resistance are not fully understood. To explore variation to pathogen infection, we used 188 Drosophila Genetic Reference Panel lines to perform a genome-wide association analysis for variation to infections with the fungus Metarhzium anisopliae (Ma549). We found substantial individual variation in within-host growth and host life span (LT50’s ranged from 3.3 to 7.2 days), with males typically being more resistant than females, and resistant lines restraining fungal growth compared to susceptible lines suggesting that tolerance is less important than resistance in determining natural variation. We found Ma549 LT50’s were moderately correlated with resistance to the bacterium Pseudomonas aeruginosa, In addition we found significant correlations with previously published phenotypes including oxidative stress sensitivity, sleep duration and number of "naps", and hemolymph glucose levels. The majority of polymorphisms affecting disease resistance had moderately large effects and were rare, suggesting that there is a general cost to defense involving trade-offs. Nevertheless, disease resistance was not correlated with longevity and fecundity. Many of the genes tagged by the top variants had plausible roles in host defense including components involved in hemocyte migration and phagocytosis, cuticle development, morphogenesis and tissue repair, glycerolipid metabolism, and protein phosphorylation. Several of the candidate genes have human homologs that were identified in studies of human disease, suggesting that genes affecting variation in susceptibility are conserved across species.