TThe current review on Pasteurella multocida and Mannheimia haemolytica tried to shed light on these two organisms due to their medical and economic importance as well as to their elevating antibiotic resistance rate among the isolates from animals basically cattle, sheep, and goats. In this comprehensive review, we screened both old and recently published works that are available electronically on authorized scientific sites. Here we provide the latest data on those organisms their structure, suitable growth conditions, virulence factors, pathogenesis, their associated diseases, and their distribution along with antibiotic resistance emergence and the possibility of more new emergences of resistant isolates among species of both organisms. Lastly, we reviewed all the old and modern methods for diagnosis, controlling, and preventing the occurrence of diseases caused by these organisms besides studying and reviewing the effective ways to manage antibiotic resistance issues. Our review concluded that more specific research is needed to shed light on phenotype and genotype differences among those organisms, some issues should be subjected to intensive investigations and research focus such as emerging and re-emerging infectious diseases caused by these organisms and antigenic variants between agents. Evaluation of innate and adaptive immunity after infections or vaccinations is important for producing more specific drugs or vaccines in the future.