Biotic and abiotic stresses severely affect the crop plants reducing yield and quality posing a huge global threat to food security. It is difficult to develop durable resistance in host plants against plant pathogens by targeting R genes using conventional breeding techniques. With the advancement in biotechnology and molecular biology, targeting susceptibility inducing genes and modifying their promoter regions or native gene structure by insertions and deletions of base pairs using genome editing techniques has proven to be an effective way to design stress resistant crops for achieving self-sufficiency in food production. However abiotic stresses like drought, salinity, temperature and heavy metal toxicities also account for huge loss of crop yields. Understanding the physiological and metabolic pathways responsible for developing abiotic stresses in plants and by targeting several transcriptional factors, enzymes and other stress related genes impart abiotic stress tolerance in plants. Novel genome-editing technologies offers a best possible way of developing biotic and biotic stress resistant cultivars which inturn make a way to achieve climate smart agriculture. Site-directed mutagenesis, zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindrome repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) are some of the most important genetic tools of recent years found to be very helpful. Considering its adaptability, cost of designing, ease in development, deployment, and greater success rate, CRISPR/Cas9 has been reported as an effective genome editing technology. The application of genome-editing techniques for the production of transgene-free biotic and abiotic stress resistant varieties is the subject of this chapter.