In this chapter, you will learn what chaperone-mediated autophagy (CMA) is, how it is different from other forms of autophagy, and what the CMA substrates are. You will also learn about the CMA effectors and regulators and how they function together to modulate CMA activity under physiological conditions. You will learn how CMA plays an essential part in protein quality control in every cell and tissue in addition to the proteasome and other forms of autophagy. While damaged proteins are degraded by CMA, you will learn that, by degrading functional undamaged proteins, CMA regulates diverse cellular processes in which those proteins participate in. You will learn about the functions of CMA in different tissues, and how malfunction of CMA contributes to specific disease conditions and aging. Finally, you will learn that restoration of CMA in old organisms serves as an anti-aging intervention and a potential therapeutic tool against age-related disorders such as neurodegeneration, retinal degeneration, and atherosclerosis.