Prophylactic vaccination against tuberculosis with BCG gained much of the credit for the decline of TB in Europe. However, with TB resurgent in many parts of the world, better vaccines are urgently needed. To improve on BCG, a rapid, rational approach to vaccine discovery is needed. Fortunately, advances in the fields of molecular biology and computer science have spawned new disciplines: Genomics, Proteomics and Transcriptomics are transforming the ways in which candidate vaccine antigens are discovered. In this review, we discuss how these new approaches have accelerated the pace of antigen discovery and vaccine development, and highlight some of the most promising new candidate vaccines and vaccine targets.