Myotonic dystrophy type I (DM1) is a severe, progressive, and debilitating condition which affects a range of human/mammalian physiological systems, including skeletal, muscular, cardiac, and neural. DM1 is the most common form of adult muscular dystrophy with a global incidence of over 1 in 8,000 people, and there is no treatment currently available. The genetic basis of DM1 is a CTG trinucleotide repeat sequence in the 3 ′ untranslated region of the dystrophia myotonica protein kinase (DMPK) gene. While the faulty DNA is correctly transcribed into RNA and spliced, it is too large to leave the nucleus and instead gets trapped there, sequestering muscleblind-like and other cell proteins to form distinct microscopically detectable nuclear foci. Being an RNA disorder, DM1 lacks a clear protein target for drug development; however, cyclin-dependent kinase 12 (CDK12) has recently been identified as a potential target. CDK12 is a ∼164 kDa protein comprising 1,490 amino acids that is located in human chromosome 17q12 and is composed of 14 exons. CDK12 is involved in the transcription of elongated RNA sections, resulting in mutant CUG RNA repeats. The inhibition of CDK12 reduces the transcription of faulty RNA and therefore could potentially treat DM1. Furthermore, the development of CDK12 inhibitors could be used to treat other disorders and even some cancers. Novel small-molecule CDK12 inhibitors remove nuclear foci and improve myotonia in patientderived cell lines and a mouse model. Selectivity for CDK12 over other proteins, such as CDK9, is achieved via the formation of a covalent bond with the cysteine 1039 residue within CDK12.