Whole sediment toxicity identification evaluation (TIE) methods were developed primarily in the late 1990s and early 2000s in research programs dedicated to developing manipulations and endpoints to characterize and identify causes of toxicity to benthic freshwater and marine organisms. The focus of these methods included nonionic organic contaminants, cationic and anionic metals, and ammonia. This chapter discusses innovations in whole sediment TIE manipulations and endpoints developed primarily over the last 10 years. Innovations such as the use of supercritical fluid extraction as a Phase III manipulation, Phase II methods for identifying pyrethroid, organophosphate, and carbamate pesticides, and the integration of genomic endpoints into the TIE structure are described. In North America, recently implemented environmental regulations require the diagnosis and identification of environmental stressors as part of the total maximum daily loading process. These regulations are likely to result in an increase in the conduct of whole sediments TIEs and encourage the development and application of more innovations.