The general stress response provides a pathway for bacteria to survive in response to a range of different environmental stresses. This pathway is largely controlled at the post-translational level through the regulated degradation of the transcription factor, SigmaS (σ^S). Under normal conditions, the phosphorylated adaptor protein RssB recognises σ^S and delivers it to the ClpXP protease where it is rapidly degraded. In contrast, under conditions of “general” stress the turnover of σ^S is inhibited by a number of stress-specific anti-adaptors, which as the name suggests inhibit the activity of the adaptor protein, RssB. Currently, three anti-adaptors have been identified in Escherichia coli. However, the molecular details of their interactions with RssB remain poorly defined. Likewise the interaction of RssB with its substrate σ^S is also poorly defined. Here we describe the mechanism by which σ^S is recognised by RssB and delivered to ClpXP for degradation. Moreover, we have identified that each anti-adaptor using a distinct mode of action to inhibit the turnover of σ^S. Collectively, these data improve our understanding of the general stress response and more specifically the mechanisms used to control σ^S turnover.