This article outlines the mechanisms involved in specific cyclooxygenase-l (COX-1) and cyclooxygenase-2 (COX-2) inhibition as they relate to the safety of nonsteroidal anti-inflammatory drug (NSAID) use. New advancements in COX-2 technology appear to improve the safety profile of NSAID therapy. Gastroenterologic issues such as ulcer disease and liver disease as related to .these novel new medications are reviewed.