In recent years, there has been significant progress in the ability to predict the three-dimensional structure of proteins from their amino acid sequence. Progress has been due to new methods to extract the growing amount of information in sequence and structure databases and improved computational descriptions of protein energetics. This review summarizes recent advances in these areas and describes a number of novel biological applications made possible by structure prediction. Despite remaining challenges, protein structure prediction is becoming an extremely useful tool in understanding phenomena in modern molecular and cell biology.