Hydrogen isotope labeling has become an area of special synthetic interest due to the widespread application of isotopic-enriched molecules in different key research disciplines, especially related to life sciences. However, the synthesis of these molecules is far from being trivial. Thus, the design of robust and efficient synthetic routes that allow the access to these appealing organic scaffolds is a task of utmost importance. Among the plethora of developed labeling strategies, hydrogen isotope exchange (HIE) methods by homogeneous transition metal (TM) catalysts stand out by their versatility and utility. This review showcases the recent advances on TM-catalyzed CH deuteration and tritiation of organic frameworks.