The role of anharmonic effects in the vibrational spectroscopy of small biological molecules and their 1 ∶ 1 complexes with water is discussed. The strengths and limitations of the vibrational self-consistent field (VSCF) method and its extensions as a computational tool for this purpose are examined. Anharmonic coupling between different vibrational modes is found to be very important for these systems, even for fundamental transitions, and incorporation of these effects seems essential for quantitative interpretation of experimental data. Both analytical, empirical force fields, and potential surfaces computed from electronic structure methods are used in VSCF calculations of several benchmark systems and compared with experimental spectroscopic data. Glycine in several conformers, the glycine–water complex, and N-methylacetamide are among the systems discussed. The main conclusions are: (1) Electronic structure methods such as MP2/DZP and density functional B97, give very good agreement with experimental data. Thus, MP2 and B97 clearly provide an accurate description of the anharmonic interactions. VSCF calculations, including all modes, with MP2, B97 and other successful methods are presently feasible for molecules with up to 15-20 atoms. (2) The electronic structure methods seem to give spectroscopic predictions in much better accord with experiment than standard empirical force fields such as AMBER or OPLS. The anharmonic couplings provided by these methods differ greatly, in the cases tested to date, from the ab initio ones. The implications of these results for future modeling of small biomolecules are discussed. Comments are provided on future directions in this subject, including extensions to large biomolecules.