Ultra-high vacuum (UHV) surface science has a long, successful history in the fields of catalysis and microelectronics. The early adaptation of UHV-based tools in these fields was largely due to the fact that the materials involved (metals, ceramics, semiconductors, etc.) were readily vacuum compatible. This talk will address the challenges of adapting UHV surface analysis techniques for analyzing organic and biological materials. These include their higher vapor pressure, their increased susceptibility to X-ray, electron, and ion sample degradation, and vacuum induced changes in their structure. Some of the first organic surface analysis experiments were done on polymers. Since that time, these experiments have been extended to self-assembled monolayers (SAMs), biomaterials, and adsorbed biomolecules. Examples to be discussed from these areas will include the effect of polymer additives, surface rearrangement of polymers, the well-defined structure of SAMs, and preserving the conformation of adsorbed proteins.