This review highlights the recent developments of the Rayleigh equation approach for quantifying in situ degradation of organic pollutants in contaminated aquifers. The advantages and limitations of the Rayleigh equation approach are discussed and suggestions for improvements are given. Concepts are provided to estimate the uncertainty due to errors or variability of input parameters and how to deal with such uncertainty. Moreover, the applicability of the Rayleigh equation approach is evaluated regarding the heterogeneity and complexity of groundwater systems. For such systems, the review discusses the relevance of non-destructive processes, which affect the concentration (e.g., dispersive mixing) and potentially also the stable isotope ratio of contaminants (e.g., sorption, volatilization), and the resulting implications for the Rayleigh equation approach.