In this chapter, strategies for elucidation of degradant structures and degradation pathways are discussed. The emphasis is placed on the use of the liquid chromatography-mass spectrometry (LC-MSn) molecular fingerprinting technique (n is typically 1 to 4) in conjunction with mechanism-based stress studies and nuclear magnetic resonance (NMR) spectroscopy. Typically, samples are first analyzed using LC-MSn, through which parent ions, major fragments, and their structural relationship with respect to those of the active pharmaceutical ingredient (API) can be established. Based on the LC-MSn molecular fingerprinting results, a possible degradation mechanism may be inferred. A particular type of stress study (forced degradation) of the API is then designed and carried out accordingly. The formation of the degradant in the stress study can be confirmed by LC-MSn by matching the LC-MSn molecular fingerprints between the stress-generated degradant and the one observed in the original sample. Sufficient quantities of the degradant can be generated for various 1D and 2D NMR analyses for further structure elucidation or verification if necessary. Using the elucidated structures of the degradants and their intermediates, the degradation pathways of the drug can be proposed. This effective approach has been demonstrated by three case studies.