The pervasiveness of bacterial resistance to conventional antibiotics, particularly those associated with staphylococcal infections, has become a global epidemic. However, research involving antimicrobial peptides (AMPs) and their synthetic analogues has unearthed a potentially novel class of antibacterials for the treatment of an array of diseases caused by pathogenic bacteria, such as staphylococci. AMPs have several unique advantages over traditional antibiotics such as the projected slow emergence of bacterial resistance to these agents and their capability to modulate the host immune response to infection. Unfortunately, their susceptibility to proteolytic degradation, loss of antimicrobial activity due to serum binding or physiological concentration of salts, and toxicity to host tissues has limited their use as systemic agents thus far. Additionally, the presence of economic and regulatory obstacles has hindered the translation of AMPs, as antimicrobials, from the bench to the clinic. The present review delves further into the benefits and challenges of utilizing AMPs as antibacterial agents (particularly for staphylococcal infections), the methods which have been utilized to overcome their limitations, their successes and failures in clinical trials, and future avenues for researchers to pursue to develop AMPs as novel therapeutic allies in the treatment of bacterial infections.