With the growing threat of antibiotic resistance, researchers around the globe are seeking alternatives to stem bacterial pathogenesis. One such alternative is bacteriocins, proteins produced by bacterial species to inhibit the growth and viability of related bacterial species. With their diverse mechanisms, which include pore formation and nuclease activities, and narrow spectrum of activities, which limit their impact to only certain bacterial species, unlike many chemical antibiotics, bacteriocins offer intriguing possibilities to selectively control individual bacterial populations. Within this review, therefore, we highlight current research exploring the application of colicins and microcins, a subset of bacteriocins, with an emphasis on their activities against drug-resistant pathogens, both in in vitro and in vivo settings.