Immunotherapy, harnessing components like antibodies, cells, and cytokines, has become a cornerstone in treating diseases such as cancer and autoimmune disorders. Therapeutic antibodies, in particular, have transformed modern medicine, providing a targeted approach that destroys disease-causing cells while sparing healthy tissues, thereby reducing the side effects commonly associated with chemotherapy. Beyond oncology, these antibodies also hold promise in addressing chronic infections where conventional therapeutics may fall short. However, antibodies identified through in vivo or in vitro methods often require extensive engineering to enhance their therapeutic potential. This optimization process, aimed at improving affinity, specificity, and reducing immunogenicity, is both challenging and costly, often involving trade-offs between critical properties. Traditional methods of antibody development, such as hybridoma technology and display techniques, are resource-intensive and time-consuming. In contrast, computational approaches offer a faster, more efficient alternative, enabling the precise design and analysis of therapeutic antibodies. These methods include sequence and structural bioinformatics approaches, next-generation sequencing-based data mining, machine learning algorithms, systems biology, immuno-informatics, and integrative approaches. These approaches are advancing the field by providing new insights and enhancing the accuracy of antibody design and analysis. In conclusion, computational approaches are essential in the development of therapeutic antibodies, significantly improving the precision and speed of discovery, optimization, and validation. Integrating these methods with experimental approaches accelerates therapeutic antibody development, paving the way for innovative strategies and treatments for various diseases ranging from cancers to autoimmune and infectious diseases.