The continual destruction and renewal of proteins that maintain cellular homeostasis has been rigorously studied since the late 1930s. Experimental techniques for measuring protein turnover have evolved to measure the dynamic regulation of key proteins and now, entire proteomes. In the past decade, the proteomics field has aimed to discover how cells adjust their proteomes to execute numerous regulatory programs in response to specific cellular and environmental cues. By combining classical biochemical techniques with modern, high-throughput technologies, researchers have begun to reveal the synthesis and degradation mechanisms that shape protein turnover on a global scale. This review examines several recent developments in protein turnover research, emphasizing the combination of metabolic labeling and mass spectrometry.