Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has recently emerged as a cause of skin and soft-tissue infection (SSTI). In the current era of increasing CA-MRSA infections, the outpatient management of SSTIs has not been well studied. This will be a clinical trial to evaluate oral off-patent antibiotics for outpatient treatment of patients with any of the 3 main types of acute uncomplicated SSTI, i.e., abscesses, infected wounds, and cellulitis. Upon enrollment, subjects will be stratified by type of infection, and then randomized to various treatments. Subjects with an acute uncomplicated cutaneous abscess receiving incision and drainage (I&D) will be treated with Trimethoprim/Sulfamethoxazole (TMP/SMX) or placebo to determine whether the addition of an antibiotic with activity against CA-MRSA is more clinically efficacious than I&D alone. Subjects with an acute wound infection will be treated with TMP/SMX or clindamycin to determine if clindamycin, an antibiotic with activity against CA-MRSA, methicillin-susceptible Staphylococcus aureus (MSSA), and streptococci is more clinically efficacious than TMP/SMX, an antibiotic with activity against CA-MRSA and MSSA. Subjects with acute cellulitis will be treated with cephalexin/TMP/SMX or cephalexin/placebo to determine if cephalexin/TMP/SMX is more clinically efficacious than cephalexin alone. The primary objectives for each type of SSTI studied are to compare the cure rates in the per protocol (PP) population. Secondary objectives provide additional means of assessment for the clinical efficacy of the employed interventions and resolution of the infection and include describing microbiological cure, change in the dimension of erythema, composite cure, surgical procedures, invasive and recurrent infections, infections in household contacts, and time to normal activity and until analgesics are no longer used at various times in the PP/ modified intent-to-treat (mITT) populations. This is a multi-center, randomized, double-blind clinical trial in which subjects will be stratified by the type of infection and then randomized to various 7-day oral antibiotic treatments, including placebo-controlled and comparative designs. The study population will include children 13 years of age and over and adults, who weigh greater than or equal to 40 kg presenting to 5 large urban emergency departments. Therapy will start on the day of enrollment. Subjects will be evaluated upon enrollment, at 2-3 days after enrollment (OTV), at 1-3 days after the end-of-therapy (EOT), at 7-14 days after the end-of-therapy (TOC), and at 6-8 weeks after the end-of-therapy (EFV).