Purpose of Review: Atypical Mycobacterium infections are occasionally encountered in clinical practice. As a result of immune function modulation in some particular populations (i.e., transplant, immunotherapies for chronic rheumatological diseases, chronic steroid therapy), there has been an increase in the number of diagnosed cases with atypical Mycobacterium, in particular M. marinum, associated with a history of exposure to natural or artificial water systems. The aim of this study is to review recent clinical presentations, risk factors, and management of M. marinum infections in immunocompromised individuals. Recent Findings: M. marinum exposure may potentially cause skin and soft tissue infections leading to important morbidity with sometimes life-threatening complications among immunocompromised hosts. The diagnosis of this infection is frequently delayed by months due to the often-atypical clinical presentations. A common immunosuppression associated with infection is TNF inhibition secondary to novel TNF inhibitors. These patients often present with infection within the nose. This atypical clinical presentation, in contrast to the classic “fish tank granuloma” hand lesion, may be related to immunosuppressive factors. Summary: Increasing awareness of this particular nontuberculous mycobacterial infection among physicians caring for patients with potential exposure to aquatic environments may reduce the time of diagnosis to treatment and avoid further complications.