NMR studies of the antiapoptotic protein survivin have been used to determine the homodimer interface of the protein in solution and to identify residues of the protein that interact with Smac/Diablo. In solution, survivin(1−120) forms a bow-tie-shaped dimer whose interface is composed of its N-terminal residues as well as residues connecting its BIR domain to the C-terminal α helix. The solution structure resolves the controversy regarding the two possible dimer interfaces for survivin observed in X-ray crystal structures. The structural basis for the interaction between survivin and Smac/Diablo was also investigated. When Smac/Diablo or N-terminal Smac/Diablo peptide analogues are added to a solution of survivin, specific residues near α4 and β3 are perturbed. NMR experiments indicate that the peptides bind across the third β-strand of survivin in a manner similar to the way Smac/Diablo peptides bind to the BIR3 domain of X-linked IAP (XIAP).