Solid phase microextraction (SPME) is an equilibrium-based technique that enables extraction of free-fraction metabolites of exogenous and endogenous origins. SPME combines sampling, extraction, and preconcentration into a single step, significantly simplifying analytical protocols and enabling on-site use. Other unique features of this method, such as low invasiveness and negligible depletion of extracted analytes from the sample, make it an ideal tool for characterization of living systems. During in vivo sampling, extraction into SPME devices enables metabolite quenching, resulting in the capture of the labile portion of the metabolome, thus providing a true chemical snapshot of the system under study. In this chapter, an overview of the technology is presented with emphasis on the characteristic features of SPME that most benefit metabolomics in comparison to other sample preparation techniques. Different aspects of the analysis of volatile, semi-, and non-volatile metabolites are discussed, and various sampling modes and phenomena associated with coating saturation, analyte replacement, and balanced coverage are explained. Commercial and lab-made extraction phases available for polar metabolome analysis are described. Also, several exemplary applications of SPME in foodomics, exposomics, and biomedical and clinical metabolomics are reviewed. Finally, future perspectives on the use of this technology in metabolomics are presented.