The ten-eleven translocation (TET) family of dioxygenases consists of three members, TET1, TET2, and TET3. All three TET enzymes have Fe(+2) and α-ketoglutarate (α-KG)-dependent dioxygenase activities, catalyzing the 1(st) step of DNA demethylation by converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), and further oxidize 5hmC to 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). Gene knockout studies demonstrated that all three TET proteins are involved in the regulation of fetal organ generation during embryonic development and normal tissue generation postnatal. TET proteins play such roles by regulating the expression of key differentiation and fate-determine genes via 1) enzymatic activity-dependent DNA methylation of the promoters and enhancers of target genes; and 2) enzymatic activity-independent regulation of histone modification. Interacting partner proteins and posttranslational regulatory mechanisms regulate the activities of TET proteins. Mutations and dysregulation of TET proteins are involved in the pathogenesis of human diseases, specifically cancers. Here, we summarize the research on the interaction partners and posttranslational modifications of TET proteins. We also discuss the molecular mechanisms by which these partner proteins and modifications regulate TET functioning and target gene expression. Such information will help in the design of medications useful for targeted therapy of TET-mutant-related diseases.