Many acute hand and upper extremity infections should be treated as surgical emergencies to avoid stiffness, contracture, pain, and amputation. Proper treatment requires understanding of anatomy and how this influences the behavior of certain infections, common offending organisms, antibiotic treatment, management of host factors, and surgical intervention. This article reviews the microbiology, antibiotic coverage, and surgical treatment of the most common infections in the hand: paronychia, felon, herpetic whitlow, flexor tenosynovitis, deep space infections, septic arthritis, bites from humans and animals, necrotizing fasciitis, mycobacterium infections, and fungal infections. Recommendations are based on the most recent available evidence.