The combination of next-generation sequencing technologies and high-throughput genotyping platforms has revolutionized the pursuit of genetic variants that contribute towards disease. Furthermore, these technologies have provided invaluable insight into the genetic factors that prevent individuals from developing disease. Exploiting the evolutionary mechanisms that were designed by nature to help prevent disease is an attractive line of enquiry. Such efforts have the potential to generate a therapeutic target roadmap and rejuvenate the current drug-discovery pathway. By delineating the genomic factors that are protective against disease, there is potential to derive highly effective, genomically anchored medicines that assist in maintaining health.