A review with several refs. The ultimate goal in protein de novo design is the creation of novel macromols. with tailor-made receptor, sensory, and catalytic functions. Despite considerable progress in understanding basic rules of secondary structure formation and protein stability, the well known protein folding problem is still far from being solved and, in general, only a limited no. of designed proteins are folded uniquely. In this article the state-of-the-art in protein design is demonstrated on some selected examples, indicating that the construction of protein-like macromols. mimicking some essential features of natural proteins seems to be within reach. Thus, protein design and mimicry has become an interdisciplinary challenge with most intriguing perspectives. 1998 John Wiley & Sons, Inc. Biopoly 47: 63-73, 1998. [on SciFinder (R)]