Mutations in mitochondrial DNA (mtDNA) are responsible for several severe diseases that have no available cures. The multicopy nature of the mitochondrial genome means that mutations often exist in a state known as heteroplasmy, where both mutant and wild-type mtDNA are present in the same cell. The wild-type mtDNA can functionally compensate for the mutant mtDNA until a mutation threshold is reached, beyond which disease symptoms begin to manifest. Despite the interest mitochondrial genetics has generated, the double mitochondrial membrane proved to be a formidable barrier to genetic manipulation. However, in the past two decades, scientists have discovered that mtDNA could be modified by importing gene editing proteins to target specific DNA sequences. Mitochondria-targeted nucleases specifically cleave and eliminate mutant mtDNA in heteroplasmic cells and in animal models. More recently, base editors have been adapted to modify mtDNA via precise C>T or A>G transitions. Therefore, tools to modify mtDNA are, finally, a reality with the promise to revolutionize the mitochondrial genetics field. This Primer delves into mitochondrial gene editing, providing details on the selection of mitochondrial gene editing tools, best practices for designing experiments, relevant types of analyses and specific applications and limitations pertaining to the different technologies and the field.