As a great river, the Ohio is an important natural resource. It is crucial that we understand the implications that human disturbances are having on the biological integrity of this ecosystem. By monitoring current conditions and the health of this ecosystem, we may be able to identify causes of degradation and potentially determine the stability of the ecosystem to human and natural alterations. In this study, we analyzed fish data collected in 1982–1986 and 2001–2005 to characterize the current fish assemblage around William H. Zimmer Power Plant, Moscow Ohio and investigate any long-term (past 20 years) and short-term (past 5 years) effects of disturbance in this area. During these two 5-year study periods, over 30,000 individuals were collected comprising 12 families and 60 species. We found that many metrics of the Ohio River Fish Index have improved over the past 20 years and the fish assemblages have remained stable over the past 5 years. Despite apparent stability, we found a decrease in invertivores and detritivores over the past 20 years and a declining trend in the Shannon-Weiner Diversity Index over the past five years. Data suggest a potential negative trend in the biological integrity of this area. The need for more data concerning the possible negative impacts of human disturbance on fish assemblages in this area of the river is apparent.