Freshwater is increasingly becoming a finite resource in many regions of the world. Gaps between estimated water supply and demand continue to narrow and the prospects of acquiring additional sources of freshwater remain limited. Furthermore, economically efficient water resource management practices are perplexed by increasing urbanization and changing land-use in semi-arid regions. Although repeated use of water is a practical and effective means for easing strain on water supplies, there is concern that unnecessary contamination may diminish future value of this important resource. Some surface waters in semi-arid regions of the U.S. are effluent-dominated as flow is comprised of >90% treated wastewater. Ionizable compounds are chemicals often associated with urban development and examples include pharmaceuticals, agrochemicals, natural toxins, and other common contaminants (e.g. ammonia). Because continued population growth and urbanization are likely to increase contaminant release and alter dilution capacity of receiving systems, it is important that best management approaches are developed at the watershed scale to limit water quality degradation associated with ionizable compounds. Current methods for prospective and retrospective ecological risk assessments of ionizable compounds seldom consider site-specific conditions during the analysis of effects of phase. Ionization state is largely controlled by the acid/base dissociation constant (pKa) and pH of the solution where a compound resides. Stream water quality can therefore influence ionization state, which is important because the unionized forms a more lipophilic and have a greater propensity to cross cellular membranes. Consequently, the unionized forms are hypothetically more toxic. I completed toxicity tests in the laboratory using various contaminants as model ionizable compounds over a gradient of environmentally-relevant surface water pH and then related measured toxicological endpoints to observed pH of surface waters using both discrete and probabilistic ecological risk assessment approaches. The result of my studies clearly demonstrated that site-specific pH may influence the toxicity of ionizable contaminants. Potential modifications to conceptual frameworks of ecological risk assessment for ionizable contaminants are suggested so that uncertainty can be reduced.