Abstract: Since the discovery of crown ethers few decades ago, the synthesis and chemistry of macrocyclic compounds has attracted considerable attention due to their unusual ability to act as hosts to both neutral and ionic species. The study of host-guest phenomenon provides fundamentals of understanding about enzyme-substrate interactions in biological systems. Recent investigations disclosed that the binding power of a host is governed by the size, the shape, the rigidity, and the noncovalent interactions of the cavity. Important is the fact that highly flexible hosts often make binding entropically unfavorable. To tune the binding ability of a host, one should carefully design the host with appropriate rigidity. Despite of the fact that urea units and cyclic derivatives thereof are known to possess powerful ligating abilities which are due primarily to their highly polarized carbonyl groups, macrocycles incorporating urea as the binding groups have received limited attention compared to their polyoxa, polyoxo,and polyaza congeners.