Cephalosporins have been widely used over the last few decades (often as first-line antibiotic therapy) for numerous infections, owing primarily to their broad spectrum of microbiologic activity and favorable safety profile. Current Infectious Diseases Society of America guidelines identify a third-generation cephalosporin in combination with a macrolide antibiotic as an option for treatment of hospitalized adult patients with community-acquired pneumonia (CAP) outside the intensive care unit setting. Although ceftriaxone is a frequently used agent for CAP, increasing incidence of multidrug-resistant Streptococcus pneumoniae and concerns regarding poor outcomes associated with ineffective therapy have prompted the search for a well-tolerated treatment alternative that is effective against bacteria that can cause CAP. Ceftaroline fosamil, the prodrug of ceftaroline, is a new extended-spectrum cephalosporin that exhibits time-dependant bactericidal activity against numerous Gram-negative and Gram-positive organisms, including methicillin-resistant Staphylococcus aureus and penicillin-resistant S. pneumoniae. Notable exceptions include Pseudomonas spp. and Gram-negative organisms that produce extended-spectrum β-lactamases or carbapenemases. Two large Phase III clinical trials (FOCUS 1 and 2) reported that ceftaroline fosamil was well tolerated, with a clinical cure rate of CAP that was noninferior to that with ceftriaxone in nonintensive care unit adult inpatients with moderately severe (Pneumonia Outcomes Research Team score of III or IV) community-acquired pneumonia.