Somatic gene therapy based on nonviral and viral vectors is an attractive approach for treatment of human diseases. It has developed from preliminary animal experiments to clinical trials. Vectors and target genes used in gene therapy are mainly focused on viral, nonviral vector and single target gene or monogene and each vector system has a series of advantages and limitations. However, the application of gene therapy to human disease is currently hampered by potential hazards of methods of gene delivery, the relatively low efficiency and intracellular stability of target gene. Safety, efficacy and stability are three problems that people often met and also three principles that people should be followed in gene therapy.