Complicated intra-abdominal infections (cIAIs) are an important cause of morbidity and mortality worldwide. They are diagnosed when the initial abdominal organ infection has spread into the peritoneal space. Successful treatment relies on adequate source control and appropriate empiric antimicrobial therapy. Inappropriate antimicrobial therapy may result in poor patient outcomes and increases in healthcare costs. Current guidelines recommend several single and combination antimicrobial regimens; however, empiric antimicrobial treatment has been complicated by the increasing rates of resistant organisms, especially the extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. Additionally, the overuse of carbapenems to combat these resistant pathogens has contributed to the rise of carbapenemase-producing microorganisms, especially Klebsiella pneumoniae. This increasing resistance has prompted the development of novel antimicrobials like ceftazidime-avibactam and ceftolozane-tazobactam, whose activity extends to ESBL-producing microorganisms. Furthermore, the optimal duration of antimicrobial therapy is still unknown, and further research is necessary to find a definitive answer. This review will focus on antimicrobial therapies recommended by the current guidelines, the individual properties of these agents, appropriate duration of therapy, recent clinical trials, and place in therapy of the antimicrobial agents recently approved for the treatment of cIAIs.