In the light of the recent potentials of deuterated molecules as pharmaceuticals or even in mechanistic understanding, efficient methods for their synthesis are continually desired. CD3-containing molecules are prominent amongst these motifs due to the parallel of the "magic methyl effect": introducing a methyl group into pharmaceuticals could positively affect biological activities. The trideuteromethyl group is bound to molecules either by C, N, O, or S atom. For a long time, the preparation methods of such labeled compounds were underestimated and involved multi-step syntheses. More recently, specific approaches dealing with the direct incorporation of the CD3 group have been developed. This Review gives an overview of the methods for the preparation of CD3-labeled molecules from conventional functional group interconversion techniques to catalytic approaches and include radical strategy. Detailed reaction mechanisms are also discussed.