The reaction of CH₄ with chlorine (Cl) radicals in the atmosphere is associated with an extraordinarily strong isotopic fractionation, where ¹²CH₄ reacts about 70 ‰ faster with Cl than ¹³CH₄. Therefore, although the Cl-based sink of CH₄ constitutes only a small contribution to its total removal rate, the uncertainty in this small sink has been identified as one of the two largest uncertainties of isotope-based CH₄ source apportionment at the global scale. The uncertainty arises from the fact that Cl levels in the atmosphere are so low that they cannot be detected directly. One very sensitive indirect method to identify and quantify the CH₄ + Cl reaction in the atmosphere is the detection of the extremely ¹³C-depleted reaction product carbon monoxide (CO) from this reaction. This article reviews the concept of this approach, its successful application in the atmosphere, its challenges and opportunities for identifying and quantifying Cl-based removal of CH₄ at the regional and global scale and its potential to detect and evaluate possible attempts to enhance CH₄ removal from the atmosphere.