Gene therapy has emerged as a potent and cutting-edge therapeutic platform for non-hereditary diseases such as viral, bacterial, and protozoal infections. Approaches for the application of gene therapy, against these pathogenic infections, include modulating host immune responses, delivering therapeutic antibodies, perturbing pathogenic genomes, and engineering vector or organisms that could prevent pathogen transmission. Recent advances in genome editing tools, such as CRISPR/Cas systems, base editors, and prime editors, allow the precise manipulation of pathogen or host genetic sequences primarily to stop replication of the pathogen, eliminate its reservoirs, and to prevent immune evasion. Adoptive cell therapies, such as CAR-T and TCR-T, have been developed to improve pathogen-specific immune clearance while RNA interference techniques and CRISPR-guided RNA targeting are being used for post-transcriptional suppression of viral and bacterial transcripts. Furthermore, antibody gene transfer, synthetic gene circuits, and vector-based cytokine delivery are being used for the restoration of dysregulated immune pathways and the induction of long-lasting immunity against various pathogenic organisms. Additionally, gene drives in disease-transmitting mosquitoes, such as in malaria, highlight a prominent example of a population-level gene therapy intervention, that offers a revolutionary approach to long-term control of vectors transmitting the pathogens. Collectively, these therapeutic approaches offer promising avenues for both preventive and therapeutic interventions while redefining treatment paradigms for non-hereditary diseases.