The major problem associated with production of transgenic proteins in plant expression systems is the low level of their accumulation. Transplastomic plants with a transgene incorporated not in the nuclear but in the plastid genome (plastome) in some cases ensure elevation of the yield of the desired protein dozens of times and more. However, two problems arise in this case: low frequency of integration of transgenes into the plastid genome and difficulties with production of homoplastomic and homoplastidic plants. Recently, a number of tendencies to overcome these difficulties have been outlined. The first problem is being solved via an improvement of the systems of delivery of exogenous DNA and a fine design of the vectors and the second by multistep screening on several antibiotics and the use of dedifferentiated tissues for transformation. This review deals with a detailed analysis of these problems and their solution.