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Genetic networks are surprisingly robust to perturbations caused by new mutations. This robustness is conferred in part by compensation for loss of a gene’s activity by genes with overlapping functions, such as paralogs. Compensation occurs passively when the normal activity of one paralog can compensate for the loss of the other, or actively when a change in one paralog’s expression, localization, or activity is required to compensate for loss of the other. The mechanisms of active compensation remain poorly understood in most cases. Here we investigate active compensation for the loss or reduction in expression of theSaccharomyces cerevisiaegeneTDH3by its paralogTDH2.TDH2is upregulated in a dose-dependent manner in response to reductions inTDH3by a mechanism requiring the shared transcriptional regulators Gcr1p and Rap1p.TDH1, a second and more distantly related paralog ofTDH3, has diverged in its regulation and is upregulated by another mechanism. Other glycolytic genes regulated by Rap1p and Gcr1p show changes in expression similar toTDH2, suggesting that the active compensation byTDH3paralogs is part of a broader homeostatic response mediated by shared transcriptional regulators.