Colibacillosis is the most prevalent infectious microbe affecting avian species resulting in financial losses. Also, Colibacillosis is frequently one of the most common illnesses mentioned in surveys regarding the health of poultry or complaints made during processing. Colibacillosis denotes any systemic or localized infection induced partly or entirely by avian pathogenic Escherichia coli (APEC), which includes coli-septicemia, coli-granuloma (Hjarre's disease), air sac disease [chronic respiratory disease (CRD)], venereal colibacillosis (acute vaginitis in turkey), swollen-head syndrome, and coliform cellulitis, peritonitis, salpingitis, osteomyelitis/ synovitis, pan-ophthalmitis, omphalitis, enteritis and lymphocytic depletion of the bursa and thymus. Often colibacillosis is among the most frequently reported diseases in surveys of poultry health or condemnations at processing. The majority of APEC isolated from chickens are certain types that are only harmful to birds and pose little risk of infection to other animals or humans. Recently, avian colibacillosis has a wide range of multidrug resistance, and the world directed to the usage of antibiotic alternatives to overcome this problem. Thus, the current review on the current status of colibacillosis among poultry farms, drug resistance, and the possible solutions via using safe natural antibiotic alternatives.