The reductionist approach is prevalent in biomedical science. However, increasing evidence now shows that biological systems cannot be simply considered as the sum of its parts. With experimental, technological and computational advances, we can now do more than view parts in isolation, thus wepropose that an increasing holistic view (where a protein is investigated as much as a whole as possible) is now timely. To further advocate this, we review and discuss several studies and applications involving allostery,where distant protein regions can cross-talk to influence functionality. Therefore, we believe thatan increasing big pictureapproach holds great promise, particularly in the areas ofantibody engineering and drug discovery in rational drug design.