Chemical Exchange Saturation Transfer (CEST) is a novel MRI contrast method that uses exogenous or endogenous compounds with exchangeable protons or molecules. CEST imaging detects indirect water signal changes through saturation of these compounds, which then transfer magnetization to water. Unlike conventional magnetization transfer contrast (MTC), CEST requires slow exchange on the MR time scale to allow selective proton saturation. CEST can use various saturation techniques beyond radiofrequency (RF) saturation, such as inversion, gradient dephasing, and frequency labeling. The basic theory, design criteria, and experimental issues for exchange transfer imaging are discussed, along with a new classification of CEST agents based on exchange type. The potential of CEST is highlighted, especially for in vivo applications and human translation. CEST works by selectively saturating exchangeable solute protons, which then transfer this saturation to water protons. Due to the low concentration of solute protons, multiple saturation transfers are needed to observe a detectable effect. The saturation effect is visualized as a Z-spectrum or CEST spectrum, which shows symmetric direct saturation (DS) around the water frequency. This DS can interfere with CEST effects, which are addressed by using MT ratio (MTR) asymmetry analysis. The MTR asymmetry is calculated by subtracting right and left signal intensity ratios, which inherently assumes independent contributions of solute and water protons. Theoretical descriptions of CEST include the proton transfer ratio (PTR), which normalizes the effect per proton. The CEST effect depends on the solute proton concentration, saturation efficiency, and exchange rate, while being counteracted by the water's longitudinal relaxation rate. The saturation efficiency is approximated by a formula involving the RF field strength and exchange rate. For mobile solutes, the saturation efficiency can be approximated by a formula involving the RF field strength and exchange rate. CEST classifications include paraCEST (paramagnetic) and diaCEST (diamagnetic), based on the chemical shift difference with water. ParaCEST agents can have much higher exchange rates due to paramagnetic shift agents, while diaCEST agents have a range of 0–7 ppm. The CEST effect is influenced by the exchange rate and saturation efficiency, with higher exchange rates and saturation efficiencies leading to stronger effects. The CEST effect is also influenced by the magnetic field strength, with higher fields allowing prolonged saturation in the water pool. CEST has been applied to various compounds, including glycogen, where the exchange rate increases with temperature. The CEST effect is detectable in Z-spectra even when the exchange rate increases due to temperature changes. The CEST effect is also used to detect amide protons in tissues, with the APT (Amide Proton Transfer) effect showing positive effects in tumors and negative effects in acute ischemia. The APT effect is influenced by pH changes, with lower pH reducing the amide proton exchangeChemical Exchange Saturation Transfer (CEST) is a novel MRI contrast method that uses exogenous or endogenous compounds with exchangeable protons or molecules. CEST imaging detects indirect water signal changes through saturation of these compounds, which then transfer magnetization to water. Unlike conventional magnetization transfer contrast (MTC), CEST requires slow exchange on the MR time scale to allow selective proton saturation. CEST can use various saturation techniques beyond radiofrequency (RF) saturation, such as inversion, gradient dephasing, and frequency labeling. The basic theory, design criteria, and experimental issues for exchange transfer imaging are discussed, along with a new classification of CEST agents based on exchange type. The potential of CEST is highlighted, especially for in vivo applications and human translation. CEST works by selectively saturating exchangeable solute protons, which then transfer this saturation to water protons. Due to the low concentration of solute protons, multiple saturation transfers are needed to observe a detectable effect. The saturation effect is visualized as a Z-spectrum or CEST spectrum, which shows symmetric direct saturation (DS) around the water frequency. This DS can interfere with CEST effects, which are addressed by using MT ratio (MTR) asymmetry analysis. The MTR asymmetry is calculated by subtracting right and left signal intensity ratios, which inherently assumes independent contributions of solute and water protons. Theoretical descriptions of CEST include the proton transfer ratio (PTR), which normalizes the effect per proton. The CEST effect depends on the solute proton concentration, saturation efficiency, and exchange rate, while being counteracted by the water's longitudinal relaxation rate. The saturation efficiency is approximated by a formula involving the RF field strength and exchange rate. For mobile solutes, the saturation efficiency can be approximated by a formula involving the RF field strength and exchange rate. CEST classifications include paraCEST (paramagnetic) and diaCEST (diamagnetic), based on the chemical shift difference with water. ParaCEST agents can have much higher exchange rates due to paramagnetic shift agents, while diaCEST agents have a range of 0–7 ppm. The CEST effect is influenced by the exchange rate and saturation efficiency, with higher exchange rates and saturation efficiencies leading to stronger effects. The CEST effect is also influenced by the magnetic field strength, with higher fields allowing prolonged saturation in the water pool. CEST has been applied to various compounds, including glycogen, where the exchange rate increases with temperature. The CEST effect is detectable in Z-spectra even when the exchange rate increases due to temperature changes. The CEST effect is also used to detect amide protons in tissues, with the APT (Amide Proton Transfer) effect showing positive effects in tumors and negative effects in acute ischemia. The APT effect is influenced by pH changes, with lower pH reducing the amide proton exchange