The turnover of cellular proteins is a highly organized process that involves spatially and temporally regulated degradation by the ubiquitin/proteasome system. It is generally acknowledged that the specificity of the process is determined by constitutive or conditional protein domains, the degradation signals, that target the substrate for proteasomal degradation. In this review, we discuss a new type of regulatory domain: the stabilization signal. A model is proposed according to which protein half-lives are determined by the interplay of counteracting degradation and stabilization signals.