A computational investigation of the conformational preferences of 2-phenethylamine has been carried out with a variety-of techniques. To determine the intrinsic (in the absence of a solvent medium) conformational preferences of the 2-phenethylamine system, ab initio calculations at various levels of theory up to the MP2/6-311+G(d,p)//IMP2/6-31G(d,p) level were carried out. This is the most sophisticated level of theory that has been applied to this biologically important system to date. In the absence of a solvent medium, phenethylamines prefer a folded gauche conformation for both the charged and neutral amines, indicating a favorable interaction between the amino group and the aromatic ring. To probe the nature of this intramolecular interaction further the effects of ring substituents on the conformational preferences were studied. The results have been compared to those obtained with semiempirical and molecular mechanics force field methods. The molecular mechanics force fields employing default parameters typically performed poorly for this system, but the results were improved significantly if the electrostatic charges were replaced. The effects of aqueous solvation have also been investigated with the GB/SA and the SM2 continuum solvation models. The best agreement with experiment is obtained when the MP2/6-311+G-(d,p)//MP2/6-31G(d,p) results are combined with the SM2-calculated solvent effect. Results of nearly the same quality can be obtained if the solvent effect is calculated with the GB/SA solvation model using AM1-CM1A charges.