The biennial Siena Proteome conferences can be regarded as the cradle of the massively expanding field of proteomics. The very term 'proteome' was introduced at the 1st Siena meeting in 1994 by Marc Wilkins, and some of the most important proteomics advancements were first reported in Siena. The intervening years have seen proteomics develop into one of the most powerful approaches in biology, providing new insights into how cells, tissues and even whole organisms function at the molecular level. The 8th Siena meeting 'From Genome to Proteome: Integration and Proteome Completion' was attended by over 400 scientists. There was one Nobel lecture, eight plenary lectures, 58 invited talks and 199 posters covering virtual proteome completion, quantitative and functional proteomics, genetics and evolution, oncology, model systems, 2D gel electrophoresis, mass spectrometry methods and validation of biomarkers. As usual, the meeting was particularly fruitful in stimulating wide-ranging consideration of future perspectives.