Background: Skin and soft tissue infections (SSTIs) have become the second most common type of infection among persons residing in long-term care facilities. Objective: The purpose of this article was to review the latest information on SSTIs among the elderly, including age-related changes, challenges, and treatment strategies in the era of emerging bacterial resistance. Methods: Relevant information was identified through a search of MEDLINE (1970—April 2010), International Pharmaceutical Abstracts (1970—April 2010), and Google Scholar using the terms skin and soft tissue infection, skin and skin structure infection, cellulitis, treatment guidelines, and elderly. Additional publications were found by searching the reference lists of the identified articles. Trials published since 1970 were selected for this review if they prospectively evaluated mostly adults (≥18 years of age), included >50 patients, and reported diagnostic criteria as well as clinical outcomes in patients treated for simple or complicated SSTIs. Results: Fifty-eight of 664 identified studies were selected and included in this review. A search of the literature did not identify any prospective clinical trials that were conducted exclusively in the elderly. Information on the treatment of SSTIs in the elderly was based solely on clinical studies that were conducted in adults in general. As recommended by the Infectious Diseases Society of America (IDSA) 2008 update, SSTIs should be suspected in elderly patients who have skin lesions and present with a decline in functional status, with or without fever. Patients who present with symptoms of systemic toxicity should be hospitalized for further evaluation. Current challenges in the management of SSTIs include the rapid emergence of community-acquired, methicillin-resistant Staphylococcus aureus (CA—MRSA), the emergence of macrolide-resistant streptococci within the past decade, and the lack of a reliable algorithm to differentiate potentially life-threatening SSTIs that require aggressive interventions and prompt hospitalization from those that can be managed in an outpatient setting. S aureus was the most common cause of SSTIs, being isolated in 42.8% (5015/11,723) of wounds, followed by streptococci. Common SSTIs in the elderly such as shingles, diabetic foot infections, infected pressure ulcers, and scabies, and their treatment were also discussed. Based on reviews of published trials, treatment of simple SSTIs generally consisted of administration of agents with activity against S aureus and Streptococcus species such as a penicillinase-resistant β-lactam, a first-generation cephalosporin, or clindamycin. Broadening of the antimicrobial spectrum to include gram-negative and anaerobic organisms should be implemented for complicated SSTIs such as diabetic foot infections and infected pressure ulcers. Local rates of MRSA, CA—MRSA, and macrolide-resistant streptococci should be considered when selecting empiric therapy. Conclusions: A search of the literature did not identify any prospective clinical trials on the treatment of SSTIs in the elderly; therefore, it is recommended to follow treatment based on the current IDSA guidelines. More research and publications are needed to establish proper selection of antimicrobial agents, treatment strategies, and duration of therapy of SSTIs in the elderly population.