Since its rise during the last two decades, gene therapy has become one of the most promising frontiers of recent biomedical research and an approach to the treatment, control or curing a great variety of genetic and acquired diseases. This chapter aims to highlight new components that have turned the whole field upside down—from better vector engineering through powerful editing tools to entirely new RNA-based technologies. There has been considerable recent advancement of viral vectors from AAV to lentivirus systems which has increased overall efficacy, tissue specificity and safety profile. Concomitant advances in non-viral delivery systems, for example lipid nanoparticles and polymer based carriers have expanded therapeutic access without eliciting immunity. One of the most revolutionary advances in recent years is the development of genome editing technologies. Gene editing using CRISPR/Cas systems, base editors, prime editors and CRISPR-associated transposases has displayed much higher accuracy in correcting pathogenic mutations. Especially, development of RNA-based therapeutics such as siRNA, antisense oligonucleotides and mRNA-replacement emerged as a versatile and reversible method to modulate gene expression in the absence of genome modification. The chapter also discusses the emerging clinical applications, regulatory decisions and pioneering case examples evidencing impact. Finally, it discusses present limitations including off-target effects, immunotoxicity, cost restriction and ethical issues. These developments collectively place gene therapy as a rapidly emerging field that will define the approach to personalized medicine for foreseeable years.