This year's Pipeline Report profiles 32 compounds that are the early fruit of pharma's investment in targeted drug design. In diabetes, HIV, hepatitis C-and especially oncology-vibrant R&D is set to revolutionize treatment with new classes of drugs over the coming decade. We spotlight today's geeky names-the DPP-IVs and MK-0518s, the Tykerbs and Telaprevirs-that are most likely to be tomorrow's glam blockbusters. Even the year's downers-we're still waiting on Acomplia, Exubera is failing to live up to the hype-are reminders of how improvements in drug development, such as Phase 0, are helping industry in its drive to become more effective. Although riskier than squeezing me-too drugs out of proven products, targeted R&D is lighting pathways not only to cures of killer diseases but to a fresh paradigm of progress and profits, and to renewed confidence in the pharmaceutical industry. From where we stand, the future looks bright.