The structure of the antimalarial drug halofantrine is analyzed by means of density functional theory (DFT) calculations, IR, and Raman spectroscopy. Strong, selective enhancements of the Raman bands of halofantrine at 1621 and are discovered by means of UV resonance Raman spectroscopy with excitation wavelength . These signal enhancements can be exploited for a localization of small concentrations of halofantrine in a biological environment. The Raman spectrum of halofantrine is calculated by means of DFT calculations . The calculation is very useful for a thorough mode assignment of the Raman bands of halofantrine. The strong bands at 1621 and in the UV Raman spectrum are assigned to combined stretching vibrations in the phenanthrene ring of halofantrine. These bands are considered as putative marker bands for interactions with the biological target molecules. The calculation of the electron density demonstrates a strong distribution across the phenanthrene ring of halofantrine, besides the electron withdrawing effect of the Cl and substituents. This strong and even electron density distribution supports the hypothesis of stacking as a possible mode of action of halofantrine. Complementary IR spectroscopy is performed for an investigation of vibrations of polar functional groups of the halofantrine molecule.