The key to a healthy mammalian cell lies in properly functioning proteolytic machineries called proteasomes. The proteasomes are multisubunit complexes that catalyze the degradation of unwanted proteins and also control half-lives of key cellular regulatory factors. Aberrant proteasome activity is often associated with human diseases such as cancer and neurodegeneration, and so an in-depth understanding of how it is regulated has implications for potential disease interventions. Transcriptional regulation of the proteasome can dictate its abundance and also influence its function, assembly, and location. This ensures proper proteasomal activity in response to developmental cues and to physiological conditions such as starvation and oxidative stress. In this review, we highlight and discuss the roles of the transcription factors that are involved in the regulation of the mammalian proteasome.