Cyclams are 14-membered tetraamine macrocycles which bind strongly to a wide range of metal ions. Medical interest has centred on clinical trials of a bicyclam for the treatment of AIDS and for stem cell mobilization, and on adducts with Tc and Cu radionuclides for diagnosis and therapy. Other potential applications particularly for Cr, Mn, Zn, and Ru cyclams are also emerging. We discuss in this critical review the mechanism of metal complexation, stability of metal cyclams and their structures, with particular emphasis on the variety of configurational states which metal cyclams can adopt. Understanding the factors which control the thermodynamics and kinetics of the interconversion of configurational states of metallo-cyclams may be a key factor in designing novel cyclam derivatives for future use in medicine. (136 References.)