Mid-IR and Raman spectroscopy are versatile tools in pharmaceutics and biopharmaceutics, with a wide field of applications ranging from characterization of drug formulations to elucidation of kinetic processes in drug delivery. After an introduction to the basic principles of IR and Raman spectroscopy, new developments in applications of these methods for studying drug delivery systems, in particular topical drug delivery, will be reviewed. FTIR-ATR is a well-established standard method used to study drug release in semisolid formulations, drug penetration, and influence of penetration modifiers; it is also capable of in vivo studies. FTIR-PAS has been applied to measure drug content in semisolid and solid formulations, to determine drug penetration into artificial and biological membranes. The big advantage of this technique is the possibility of spectral depth profiling. However, FTIR-PAS is so far limited to in vitro investigations. Raman spectroscopy can be used to characterize the structure of colloidal drug carrier systems. Raman spectroscopy is readily applicable to in vivo studies, but such investigations must fulfill the relevant laser safety guideline. Recently, there has been tremendous technical improvement in vibrational microspectroscopy. FTIR imaging shows great promise in its ability to visualize the drug and excipient distribution in pharmaceutical formulations such as tablets and therapeutic transdermal systems, as well as to reveal the mechanism of drug release. Furthermore, this unique technique offers completely new possibilities to study the lateral diffusion of drugs.