The functional requirement to form and maintain the active site structure probably exerts a strong selective pressure on a protein to adopt just one stable and evolutionarily conserved fold. Nonetheless, new evidence suggests the likelihood of protein fold being neither physically nor biologically invariant. Alternative folds discovered in several proteins are composed of constant and variable parts. The latter display context-dependent conformations and a tendency to form new oligomeric interfaces. In turn, oligomerisation mediates fold evolution without loss of protein function. Gene duplication breaks down homo-oligomeric symmetry and relieves the pressure to maintain the local architecture of redundant active sites; this can lead to further structural changes.