Despite great advances in molecular dynamics simulations, there remain large gaps between the simulations and experimental observations in terms of the time and length scales that can be approached. Developing fast and accurate algorithms and methods is of ultimate importance to bridge these gaps. In this Account, we briefly summarize recent efforts in such directions. In particular, we focus on integrated tempering sampling. The efficiency of this sampling method has been demonstrated by applications to a range of chemical and biological problems: protein folding, molecular cluster structure searches, and chemical reactions. The combination of integrated tempering sampling and a trajectory sampling method allows the calculation of rate constants and reaction pathways without predefined collective coordinates.