In this paper, we report the molecular modeling of the 5HT2A receptor and the molecular docking of arylpiperazine-like ligands. The focus of the research was on explaining the effects the ligand structure has on the binding properties of the 5HT2A receptor and on the key interactions between the ligands and the receptor-binding site. To see what the receptor–ligand interactions were, various substituents were introduced in one part of the ligand, keeping the rest unchanged. In this way, using a docking analysis on the proposed 5HT2A receptor model, we identified key receptor–ligand interactions and determined their properties. Those properties were correlated with experimentally determined binding affinities in order to determine the structure to activity relationship of the examined compounds.