Diminished oxygen supply to tissues (hypoxia) can stem from many sources, and is a contributing factor to diverse disease processes. Cell and tissue responses to hypoxia are diverse and include dramatic changes in metabolic demand, regulation of cellular gene products, and release of lipid and protein mediators. Surprisingly little attention has been paid to targeted development of therapeutics for hypoxia-related disease processes. This review will focus on recent advances in cellular and molecular biology pertaining to the hypoxia response, and will discuss paradigms used to study hypoxia and the potential targets for therapeutic intervention.