Avian colibacillosis, caused by Escherichia coli, is one of the major bacterial diseases in the poultry industry worldwide, and along with salmonellosis, it is the most common avian disease communicable to humans. The organism is a normal inhabitant of the intestinal tract of birds and can survive in a wide range of temperature. Certain strains viz., avian pathogenic E. coli (APEC), however, could spread to various internal organs and cause colibacillosis characterized by fatal systemic disease. Faeco-oral route is the main mode of infection, though vertical transmission is also possible. The disease occurs in various forms in poultry: colisepticemia and acute septicemia, air sac disease, pericarditis, perihepatitis, Mushy chick disease (yolk sac infection), peritonitis, panopthalmitis, synovitis, salpingitis, bumble foot, cellulitis, swollen head syndrome, infectious asthenia, and Hjarre’s disease. Increased cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) due to E. coli infection affect the absorption of sodium as well as chloride and water balance ultimately producing watery diarrhea and death. APEC isolates also are of potential concern for public health professionals. Infected persons usually manifest diarrhea which may be complicated by other syndromes depending on the serotype. Diagnosis is based on isolation and growth characteristics of the organism in wide variety of bacteriological media, biochemical tests, serological assays, enzyme linked immunosorbent assay (ELISA), molecular tools of polymerase chain reaction (PCR) and its various versions, phylogenetic analysis and other techniques. The disease must be differentiated from a wide variety of other bacterial diseases. Antibiotic sensitivity test is useful to select proper antibiotic but plasmid mediated resistance do occur for which vitamin as well as probiotic and bacteriophage therapy are gaining much attention nowadays. Live and inactivated mutant vaccines are available. Proper hygiene and sanitation along with good hatchery management are the prerequisites to prevent the occurrence of disease. Different disease manifestations caused by APEC, insights into this economically important avian pathogen, epidemiology, trends and advances in diagnosis, prevention and control, novel and emerging therapeutic regimens, and the associated public health concerns envisage the topic of discussion in the present review.