Compound-specific isotope analysis (CSIA) is an advanced characterization tool increasingly used by field practitioners to demonstrate degradation of compounds such as benzene, toluene, ethylbenzene, and xylene (BTEX) in petroleum hydrocarbon-contaminated aquifer systems. Formerly used to demonstrate occurrence of in situ biodegradation of BTEX during natural attenuation in groundwater, CSIA underwent substantial research and development to confidently be applied in the frame of engineered remediation efforts. Due to the feasibility to demonstrate destruction of contaminants by tracking the change in isotopic composition caused by either biotic or abiotic processes, mass destruction process initiated by the remediation treatment can be distinguished from other co-occurring non-destructive mass removal process(es) such as sorption and dilution. For this reason, CSIA has become a valuable characterization tool to directly assess the performance of the remediation treatment on specifically selected contaminants. This chapter presents the principles of CSIA application to assess performance of in situ remediation treatments applied to BTEX-contaminated sites. The information introduced herein on CSIA is presented from the perspective of supporting field practitioners in their intention to implement the tool at field sites.