Bacteriophages (phages) or bacterial viruses have long been proposed as an alternative therapy against antibiotic-resistant bacteria such as Escherichia coli. Even though poorly documented in the scientific literature, a long clinical history of phage therapy in countries such as Russia and Georgia suggests potential value in the use of phages as antibacterial agents. Escherichia coli is responsible for a wide range of diseases, intestinal (diarrhoea) and extraintestinal (UTI, septicaemia, pneumoniae, meningitis), making it an ideal target for phage therapy. This review discusses the latest research focusing on the potential of phage therapy to tackle E. coli-related illnesses. No intact phages are approved in EU or USA for human therapeutic use, but many successful in vitro and in vivo studies have been reported. However, additional research focused on in vivo multispecies models and human trials are required if phage therapy targeting E. coli pathotypes can be a story with happy end.