Replication-deficient viruses have been used most successfully in the field of gene therapy because of their high transfection efficiency. However, the risk of insertional mutagenesis and induction of unwanted immune responses remains still critical for their safe application. On the other hand, nonviral vectors have been intensively investigated for plasmid DNA (pDNA) delivery as a safer alternative although their gene transfer efficiency is still many folds lower than for viral vectors, which has been predominately attributed to the insufficient transport of pDNA into the nucleus. Instead of pDNA, messenger RNA (mRNA) has recently emerged as an attractive and promising alternative in the nonviral gene delivery field. This strategy combines several advantages compared to pDNA: (i) the nuclear membrane, which is a major obstacle for pDNA, can be avoided because mRNA exerts its function in the cytoplasm; (ii) the risk of insertional mutagenesis can be excluded; (iii) the determination and use of an efficient promoter is omitted; (iv) repeated application is possible; (v) mRNA is also effective in non-dividing cells, and (vi) vector-induced immunogenicity may be avoidable. In this review, we summarize recent improvements of mRNA gene delivery and discuss its opportunities for the usage in gene therapy.