The application of a core battery of WaterTox Program toxicity tests were applied to different types of samples by three South American laboratories. Different Hazard Assessment Schemes (HAS) were developed based on existing indexes. In Colombia, the PEEP index (Costan et al., 1993) was used to compare the toxic potential of industrial wastewaters. In Chile, a ranking scheme based on approaches proposed by the National Water Research Institute of Environment Canada (Dutka, 1988; Dukta and Kwan, 1988) and Gent University, Belgium (Persoone et al., 2003) was employed to assess the toxicity of soluble contaminants associated with biosolids from municipal wastewater treatment plants. In Argentina, a classification system for water samples, the Effect-Dilution Average Ratio Index (EDAR), was utilized to assess hazardous waste, leachates, water and sediment pore waters. In this chapter, applications of these Hazard Assessment Schemes are discussed based on the ranking scale of each HAS and toxicity test responses to pure compounds subsequent to an initial round-robin exercise. Some limitations are encountered in applying the test battery especially owing to the lack of sensitivity related to insoluble toxicants. Testing samples concentrated by pre-treatment with solvents proved unhelpful, since high dilutions were then required to avoid carrier toxic effects. Overall, the application of specific HAS schemes with the WaterTox battery of toxicity tests contributed ecotoxicological information that identified the more problematic water samples and wastes in three South American countries. Such information is crucial for subsequent decision-making that will lead to improved protection and conservation of aquatic ecosystems.