Polyurethanes are one of the most important classes of polymeric materials. This is mainly due to the availability of a very large number of inherently different starting materials that allows the design and synthesis of polyurethane based materials with a wide range of properties for numerous applications. In this short review, important physical and chemical factors and parameters that have a significant effect on the properties of polyurethanes are discussed. Critical contribution of hydrogen bonding on the structure-morphology-property behavior of these materials was emphasized by both experimental data and molecular simulation studies. Influence of the chemical structures, solubility parameters and molecular weights of the soft and hard segments on morphology and properties were discussed. Important issues regarding the reaction chemistry, synthetic method used and thermal history on structure and performance of polyurethanes were explained. We hope this article, which is prepared to celebrate the 100th anniversary of Polymer Science, will be useful to those who are newcomers to the field, but also to the experienced researchers to better understand the structure-property behavior of polyurethanes and tailor-design novel structures for various applications.