Macroscopic properties of biomolecular systems are a straightforward consequence of time dependent microscopic interactions. Molecular Dynamics (MD) Simulations provide a time dependent microscopic properties of biomolecules, which could not be explained by experimental methods like X-ray crystallography. These specifications enable MD simulations as most widely used computational techniques for the study of dynamical properties of proteins, DNAs and other bio-macromolecules. In the present chapter, we focus the scopes, applicability and major case studies of MD simulations. The chapter also provides some lucid discussions about the pros and cons of free energy pathways like MM-PB (GB)/SA, LIE and other alchemical methods which are frequently used to study the binding mode of several biomolecular complexes. © 2013 by Apple Academic Press, Inc.