This review article by van Zijl and Yadav provides an in-depth look at Chemical Exchange Saturation Transfer (CEST) imaging, a relatively new MRI contrast approach. CEST involves selectively saturating exogenous or endogenous compounds containing exchangeable protons or molecules, which are then detected indirectly through the water signal with enhanced sensitivity. The authors focus on the basic magnetic resonance (MR) principles underlying CEST, comparing it to conventional magnetization transfer contrast (MTC). They discuss the similarities and differences between CEST and MTC, emphasizing that CEST requires sufficiently slow exchange on the MR time scale to allow selective irradiation of the protons of interest. The article also covers the theoretical description and spectral features of CEST, including the proton transfer ratio (PTR) and the impact of exchange rates and concentration on the CEST effect. Additionally, it explores the classification of CEST agents based on exchange type and the potential of this field for in vivo applications and translation to humans. The authors propose a new classification for CEST agents based on the exchange mechanism (atom, molecular, or compartmental exchange) and discuss the advantages and disadvantages of each class. They also delve into the competition between chemical exchange and dipolar cross-relaxation in liquids and semi-solids, and the impact of multiple molecular systems in cells and tissues on data interpretation. The article concludes with a discussion on pulse sequences for studying exchange effects and the challenges and opportunities in signal and parameter quantification, including the use of frequency-labeled exchange transfer (FLEX) for enhanced sensitivity and the importance of accurate water frequency determination.This review article by van Zijl and Yadav provides an in-depth look at Chemical Exchange Saturation Transfer (CEST) imaging, a relatively new MRI contrast approach. CEST involves selectively saturating exogenous or endogenous compounds containing exchangeable protons or molecules, which are then detected indirectly through the water signal with enhanced sensitivity. The authors focus on the basic magnetic resonance (MR) principles underlying CEST, comparing it to conventional magnetization transfer contrast (MTC). They discuss the similarities and differences between CEST and MTC, emphasizing that CEST requires sufficiently slow exchange on the MR time scale to allow selective irradiation of the protons of interest. The article also covers the theoretical description and spectral features of CEST, including the proton transfer ratio (PTR) and the impact of exchange rates and concentration on the CEST effect. Additionally, it explores the classification of CEST agents based on exchange type and the potential of this field for in vivo applications and translation to humans. The authors propose a new classification for CEST agents based on the exchange mechanism (atom, molecular, or compartmental exchange) and discuss the advantages and disadvantages of each class. They also delve into the competition between chemical exchange and dipolar cross-relaxation in liquids and semi-solids, and the impact of multiple molecular systems in cells and tissues on data interpretation. The article concludes with a discussion on pulse sequences for studying exchange effects and the challenges and opportunities in signal and parameter quantification, including the use of frequency-labeled exchange transfer (FLEX) for enhanced sensitivity and the importance of accurate water frequency determination.