In all forms of life, the amount of cellular protein present at any given time is tightly regulated by a combination of mechanisms of gene expression, namely transcription, mRNA degradation, translation, and protein degradation. A variety of events can trigger changes in protein abundance throughout the cell cycle by affecting the different steps of gene expression. Although the mechanisms that regulate gene expression in prokaryotes and eukaryotes are well known, the way in which protein abundance is controlled at each regulatory step remains unclear. The quantitation of protein levels is essential to understand the different aspects of gene expression, while a solid knowledge of the mechanisms and causes that affect protein levels should enable the development of new technologies, whether for human needs or environmental care. In the past, considerable effort has been invested in quantifying protein abundances in different situations such as stress, disease progression, or changing environmental conditions. More recently, significant advances have been made in the methods used to quantify protein abundance on the genome scale, in specific cells at certain time points, and/or under different environmental conditions. In this chapter, the different mechanisms that control protein abundance variation in prokaryotes and eukaryotes – that is, the biochemical features of mRNAs and proteins, as well as external factors such as environmental changes, stress, diseases, or developmental stages – are reviewed. Details are also be provided of the most relevant methodologies for the qualitative and quantitative analyses of protein abundance.