The success of vibrational spectroscopy in diagnosis and screening is closely dependent on the selection of right methodological approaches, which include correct sample preparation and spectral acquisition, as well as accurate data analysis, including pre-processing, statistical analysis, and complementing with different chemometric methods. Throughout this book, various aspects within these steps of infrared (IR) and Raman spectroscopy and microspectroscopy, as well as Terahertz spectroscopy, are discussed extensively. Taking this into consideration, the main concern of this chapter is to summarize methodological approaches and address a variety of practical points that are frequently encountered and need clarification during vibrational spectroscopic studies. Emphasis on computational analysis is also provided due to a lack of such a guide in the biospectroscopic literature especially targeting new starters. The focus is on describing univariate statistical analyses frequently used in biospectroscopy. Less emphasis is given on multivariate statistical analyses, because these subjects are thoroughly discussed with examples in the following chapters.