Putative treatments for the frontotemporal lobar degenerations are likely to become available for testing in clinical trials in the next few years. To design clinical trials for this group of disorders, a number of conceptual, methodologic, and diagnostic issues must be resolved. This presentation reviews diagnostic criteria, instruments for longitudinal study, questions about study duration, and the possible uses of biomarkers in clinical trials. In addition, a multicenter trial is described in which some aspects of diagnosis and longitudinal measurement in the frontotemporal lobar degenerations are being specifically explored.