There are several promising new strategies against resistance development in microbial infections. This paper discusses typical experimental and bioinformatical strategies to study the impact of infectious challenges on host-pathogen interaction, followed by several novel approaches and sources for new pharmaceutical strategies against resistance development. Genomics reveals promising new targets by providing a better understanding of cellular pathways, through the identification of new pathways, and by identifying new intervention areas, such as phospholipids, glycolipids, innate immunity, and antibiotic peptides. Additional antibiotic resources come from new genomes, including marine organisms, lytic phages and probiotic strategies. A system perspective regards all interactions between the host, pathogen and environment to develop new pharmacogenomic strategies against resistance development.