It has recently been conjectured that string theory does not admit de Sitter vacua, and that quintessence explains the current epoch of accelerated cosmic expansion. A proposed, key prediction of this scenario is time-varying couplings in the dark sector, induced by the evolving quintessence field. We note that cosmological models with varying couplings suffer from severe problems with quantum corrections, beyond those shared by all quintessence models. The vacuum energy depends on the masses and couplings of the theory, and even small variations of parameters can lead to overwhelmingly large corrections to the effective potential. We find that quintessence models with varying parameters can be realised in consistent quantum theories by either: 1) enforcing exceptional levels of fine-tuning; 2) realising some unknown mechanism that cancels all undesirable contributions to the effective potential with unprecedented accuracy; or 3) ensuring that the quintessence field couples exclusively to very light states, and does not backreact on heavy fields.