Empirical observations from fluvial systems across the globe reveal a consistent power-law scaling between channel slope and contributing drainage area. Theoretical arguments for both detachment- and transport-limited erosion regimes suggest that rock uplift rate should exert first-order control on this scaling. Here we describe in detail a method for exploiting this relationship, in which topographic indices of longitudinal profile shape and character are derived from digital topographic data. The stream profile data can then be used to delineate breaks in scaling that may be associated with tectonic boundaries. The description of the method is followed by three case studies from varied tectonic settings. The case studies illustrate the power of stream profile analysis in delineating spatial patterns of, and in some cases, temporal changes in, rock uplift rate. Owing to an incomplete understanding of river response to rock uplift, the method remains primarily a qualitative tool for neotectonic investigations; we conclude with a discussion of research needs that must be met before we can extract quantitative information about tectonics directly from topography.