Abstract: A survey will be given of the simulation methods as applied to the design of nontrivial sequences in synthetic copolymers aimed at achieving desired functional properties. A recently developed approach, called conformation-dependent sequence design (CDSD), will be described. This approach is based on the assumption that a copolymer obtained under certain preparation conditions is able to “remember” features of the original conformation in which it was built and to store the corresponding information in the resulting sequence. The emphasis will be put on copolymer sequences exhibiting large-scale compositional heterogeneities and long-range statistical correlations between monomer units. Several new synthetic strategies and polymerization processes that allow synthesis of copolymers with a broad variation of their sequence distributions will be reported. It will be shown how the preparation conditions dictate copolymer sequences. Also, we will discuss advances that have recently been achieved in the computer simulation and theoretical understanding of designed copolymers in solution and in bulk. The focus will be on amphiphilic protein-like copolymers and on hydrophobic polyelectrolytes. It will be demonstrated how copolymer sequence dictates structure and properties.