Background: Skin and soft tissue infections (SSTIs) are common presentations in the emergency department. However, this is less common after contact with contaminated saltwater or freshwater. This review presents the diagnosis and management of water-related soft tissue sepsis in this vulnerable and difficult-to-treat subgroup of necrotizing soft tissue sepsis. Methods: A summative literature overview is presented regarding bacterial and fungal SSTI after contact with contaminated water, with practical diagnostic and management aspects. Results: The literature indicates that these wounds and infections remain difficult to treat. An approach using appropriate diagnostic tools with both medical and surgical management strategies is provided. Conclusions: SSTIs due to water contamination of wounds involve unusual organisms with unusual resistance patterns, and require a nuanced and directed diagnostic approach with an adaptation of the usual antibiotic or antifungal selection to achieve a successful cure, along with aggressive debridement and wound care.