Lasso is a seminal contribution to high-dimensional statistics, but it hinges on a tuning parameter that is difficult to calibrate in practice. A partial remedy for this problem is Square-Root Lasso, because it inherently calibrates to the noise variance. However, Square-Root Lasso still requires the calibration of a tuning parameter to all other aspects of the model. In this study, we introduce TREX, an alternative to Lasso with an inherent calibration to all aspects of the model. This adaptation to the entire model renders TREX an estimator that does not require any calibration of tuning parameters. We show that TREX can outperform cross-validated Lasso in terms of variable selection and computational efficiency. We also introduce a bootstrapped version of TREX that can further improve variable selection. We illustrate the promising performance of TREX both on synthetic data and on a recent high-dimensional biological data set that considers riboflavin production in B. subtilis.