Over the last century, a great deal of effort and resources have been poured into the development of vaccines to protect against malaria, particularly targeting the most widely spread and deadly species of the human-infecting parasites: Plasmodium falciparum. Many of the known proteins the parasite uses to invade human cells have been tested as vaccine candidates. However, precisely because of the importance and immune visibility of these proteins, they tend to be very diverse, and in many cases redundant, which limits their efficacy in vaccine development. With the advent of genomics and constantly improving sequencing technologies, an increasingly clear picture is emerging of the vast genomic diversity of parasites from different geographic areas. This diversity is distributed throughout the genome and includes most of the vaccine candidates tested so far, playing an important role in the low efficacy achieved. Genomics is a powerful tool to search for genes that comply with the most desirable attributes of vaccine targets, allowing us to evaluate function, immunogenicity and also diversity in the worldwide parasite populations. Even predicting how this diversity might evolve and spread in the future becomes possible, and can inform novel vaccine efforts.