Proteins are heteropolymers built from the 20 naturally occurring amino acids. These molecules, which may contain fewer than 50 or as many as several hundred amino acids, adopt unique three-dimensional structures (folds) determined by the sequence of amino acids in the polymeric chain. In the late 1960s, C. Levinthal formulated the paradox that an impossibly long period of time is required to fold an average-sized protein by a random search of all possible conformations. The fact that proteins fold quite rapidly demonstrates that they follow folding pathways to reach to their equilibrium conformations. Understanding how proteins form their unique structures from nonnative conformations remains a challenge for both theory and experiment.