There is a clinical need for new treatment options as a result of continued increase in the expression of resistance among bacterial pathogens. A number of compounds currently in development show promise. However, in some cases, there is concern that resistance may develop quickly to new compounds that are based on existing antimicrobial agents. Therefore, daptomycin, a novel lipopeptide with a unique mode of action, is of particular interest. It has rapid bactericidal activity against growing and stationary-phase bacteria, once-daily dosing regimen, and has a low potential for the development of resistance. It has been approved for the treatment of complicated skin and soft tissue infections caused by Gram-positive bacteria, and registration for treatment of infective endocarditis and bacteraemia is anticipated. Daptomycin is a welcome addition to the antimicrobial armamentarium for the treatment of bacterial infections. Tigecycline is a new glycyclcycline antimicrobial recently approved for use in the USA, Europe and elsewhere. While related to the tetracyclines, tigecycline overcomes many of the mechanisms responsible for resistance to this class. It is a novel broad spectrum glycylcycline with good activity against Gram-positive, many Gram-negative, anaerobic, and some atypical pathogens that has been developed to address this need. It is efficacious in complicated skin and soft tissue infections and in intra-abdominal infections. This review aims to summarise the key clinical data of daptomycin and tigecycline which hold promise for widespread clinical use in the next decade.