Microbiological contamination is an important water-quality problem worldwide. Human impact on this category of contamination is significant and several human-related activities, and also the population explosion, have affected and are still affecting dramatically the aquatic environment. Extensive industrialization and agriculture have led to increased pollution and hydromorphological changes in many river basins. The Danube river is one of the most affected by these changes where human involvement is undeniable, and subsequently, the Danube Delta Biosphere Reserve became one of the most vulnerable ecosystems. This review is an attempt to analyse the microbiological contamination and to identify the major role human activities play in altering the water quality of the rivers.