Indiana University will host a workshop titled "eScience for Cheminformatics and Drug Discovery 2008." Among the topics to be covered is "grand challenges in cheminformatics."
From Wikipedia, a "grand challenge" is "a fundamental problem in science or engineering, with broad applications, whose solution would be enabled by the application of high performance computing resources that could become available in the near future." The term has also been used more loosely to mean any fundamental problem whose solution would significantly open up a field for further advance.
If you had to pick just one, what's the most important grand challenge in cheminformatics?