The ability of natural and synthetic polyampholytes to exist in globular, coil, helix, stretched, and ordered conformations is reviewed and transformations and transitions between the respective states upon variation of conditions are highlighted. The properties of polyampholytes in solution, condensed, and gel state as well as at various interfaces are discussed in order to clarify the principles of the structural organization of proteins, model the function of biomembranes, and study the biocompatibility of modified materials. Application aspects of polyampholytes in protein separation, desalination, catalysis, the oil industry, biotechnology, nanotechnology, and medicine are given.