Adsorption processes are utilized in both medicine and industry. It is important to have an understanding of adsorption processes to better predict the outcomes and discern potential difficulties. The primary objective of this research is to further the understanding of the nature and extent of the adsorption process in solution, which is a function of the chemical composition of the adsorbates, adsorbents, and solvent. This was accomplished by employing experimental studies as well as thermodynamic calculations and molecular dynamic simulations. Four activated carbons were used as the model adsorbents in this study. And, barbital, phenobarbital and primidone were used to elucidate the structural features of the adsorbates that were most responsible for the interaction with activated carbons. A Two-Mechanism Langmuir-Like Equation (TMLLE) was proposed to describe the independent presence of two adsorption mechanisms: non-site-specific adsorption and site-specific adsorption. The analyses of data generated by both previous investigators and current studies, suggest that the TMLLE allows an accurate analysis of the adsorption process. Based on the parameters in the TMLLE, the Modified Crisp Model and the van’t Hoff Model were employed to determine the Gibbs free energy changes for both site-specific adsorption and non-site-specific adsorption. Comparing the Gibbs free energy changes calculated by the Modified Crisp Model and the van’t Hoff Model (site-specific adsorption case), it is concluded that 5 water molecules are displaced by a phenobarbital molecule on the surface of activated carbons. And, for non-site-specific adsorption, it is concluded that 12 water molecules are displaced by a phenobarbital molecule on the nonpolar (hydrocarbon) part of the activated carbon surface. The adsorption of phenobarbital from solution by activated carbons has been simulated by employing Molecular Dynamic (MD) Modeling. The predicted differential Gibbs free energy values for site-specific adsorption at pH 2-9 were consistent with the thermodynamic calculations. And, the present MD simulations provide a good basis for the further understanding and quantitatively assessment of the adsorption driven by hydrophobic bonding. The conclusions reached in the current studies are expected to be applicable to a wide range of similar adsorption processes.