Bioavailability, largely due to membrane permeation, is an important step in the drug delivery process and therefore drug design. In this study, a series of molecular dynamics simulations (totaling 10's of nanoseconds) of small molecules (varying in size, and functional groups) in lipid bilayer membranes were used to elucidate the mechanism of diffusion of drugs within biomembranes. These simulations accurately reproduce many experimentally observed parameters. The simulations also agree with theory that indicates the lipid bilayer has internal structure that influences the diffusion process and that even within the hydrocarbon regions there are distinct regions between which the rate and mechanism of diffusion varies. In particular, in agreement with experiment and theory the small solutes were found to diffuse by a mechanism different from that of large molecules. These variations are linked to the frequency and size of spontaneously arising voids within the bilayer as well as the rate of torsional isomerization of the hydrocarbon chains.