A large body of work has gone into understanding the effect of mutations on protein structure and function. Conventional treatments have involved quantifying the change in stability, activity and relaxation rates of the mutants with respect to the wild-type protein. However, it is now becoming increasingly apparent that mutational perturbations consistently modulate the packing and dynamics of a significant fraction of protein residues, even those that are located >10-15 Å from the mutated site. Such long-range modulation of protein features can distinctly tune protein stability and the native conformational ensemble contributing to allosteric modulation of function. In this review, I summarize a series of experimental and computational observations that highlight the incredibly pliable nature of proteins and their response to mutational perturbations manifested via the intra-protein interaction network. I highlight how an intimate understanding of mutational effects could pave the way for integrating stability, folding, cooperativity and even allostery within a single physical framework.