The dawn of a troubling post-antibiotic era likely is on the horizon, fuelled by a rise in bacterial resistance to existing antibiotic therapy alongside a waning pipeline of novel antibacterial agents. Tigecycline, a new glycylcycline with an expanded broad spectrum of in vitro activity, was recently approved for the treatment of complicated skin and soft tissue infections (cSSTIs) and complicated intra-abdominal infections (cIAIs). This review will examine how tigecycline evades the common mechanisms of antibiotic resistance, the metabolism and pharmacokinetics of tigecycline, and its spectrum of in vitro activity. The results of randomized clinical trials for the treatment of cSSTIs and cIAIs with tigecycline are also described, as is the patient safety and tolerability observed during these studies. Tigecycline monotherapy has been shown to be as effective as its comparators and, against a backdrop of rising bacterial resistance, the role for tigecycline in monotherapy of infections from Gram-positive, Gram-negative and anaerobic bacteria is a meaningful development.