Under physiological conditions, proteins continuously fluctuate among a large number of conformational substates which can be represented by local minima in a multidimensional potential energy landscape. The complex topography of the landscape gives rise to an extremely broad distribution of characteristic times for conformational motions, spanning more than fifteen orders of magnitude, from fast bond librations to slow global unfolding. Here we focus on motions occurring on time scales larger than microseconds, which are particularly relevant to biomolecular function. For carbon-monoxy myoglobin, the photosynthetic reaction center of purple bacteria, and bovine pancreatic trypsin inhibitor, large-scale conformational changes have been measured over a wide temperature range. In all three cases, the rate coefficients governing the slow conformational changes depend strongly on temperature, and the dynamics can be understood with a model that assumes diffusional motions on a rugged energy land-scape with a random amplitude distribution around an average of about 10 kJ/mol. ©1999 American Institute of Physics.