The most difficult samples to analyze are those derived from biological sources. The analysis of biological samples requires the ability to extract and isolate a wide range of environmental pollutants from an even wider range of matrices, from simple bacteria to tissues and fluids from humans, from fungi to the complex tissues and structures of the plants and products that compose the food chain. These matrices comprise a variety of cells, connective tissues and fibers, fluids and related materials that introduce literally thousands of different organic and inorganic compounds to every analysis effort. In order to recognize and assess the nature and severity of pollution and its impact on humans as well as the flora and fauna that constitute our environment, highly efficient and selective methods for the extraction and cleanup of such samples must be developed. New developments in analytical science have been brought to bear on this problem, speeding the extraction and analysis process while making the resulting analyses more sensitive and selective. The present article examines the historical approach to the extraction and cleanup of biological samples for the analysis of pollutants, and reviews recent advances in technology and methodology that have proven applicable to this field.